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date: 17 January 2019

Neuromodulatory Feedback to the Inferior Colliculus

Abstract and Keywords

The inferior colliculus (IC) receives prominent projections from centralized neuromodulatory systems. These systems include extra-auditory clusters of cholinergic, dopaminergic, noradrenergic, and serotonergic neurons. Although these modulatory sites are not explicitly part of the auditory system, they receive projections from primary auditory regions and are responsive to acoustic stimuli. This bidirectional influence suggests the existence of auditory-modulatory feedback loops. A characteristic of neuromodulatory centers is that they integrate inputs from anatomically widespread and functionally diverse sets of brain regions. This connectivity gives neuromodulatory systems the potential to import information into the auditory system on situational variables that accompany acoustic stimuli, such as context, internal state, or experience. Once released, neuromodulators functionally reconfigure auditory circuitry through a variety of receptors expressed by auditory neurons. In addition to shaping ascending auditory information, neuromodulation within the IC influences behaviors that arise subcortically, such as prepulse inhibition of the startle response. Neuromodulatory systems therefore provide a route for integrative behavioral information to access auditory processing from its earliest levels.

Keywords: acetylcholine, dopamine, norepinephrine, serotonin, noradrenaline, auditory, midbrain

The inferior colliculus (IC) is an auditory crossroads. It receives ascending and descending inputs from auditory regions, contains functional domains defined by projections from specific auditory brainstem nuclei or by particular neurotransmitters, and responds to non-auditory events (Bajo & King, 2012; Bulkin & Groh, 2012; Choy Buentello et al., 2015; Lesicko et al., 2016; Loftus et al., 2010; Patel et al,. 2017; Zhou & Shore 2006). Projections from these different sources converge at the level of the IC to create or refine responses to acoustic stimuli. The IC further stages ascending and descending projections to auditory as well as non-auditory targets (Bartlett, 2013; Coomes & Schofield, 2004; Ito et al., 2009; Peruzzi et al., 1997; Schofield & Cant, 1999). Because of its centrality to these converging and diverging pathways, the IC is an important site for regulatory control.

There is a growing appreciation that regulation of the excitatory-inhibitory circuitry in the IC and other auditory regions can allow auditory processing to dynamically adjust to behavioral context, internal state, or experience (Charitidi & Canlon, 2010; Hurley & Hall, 2011; Weinberger, 2015). One important mechanism underlying this type of regulation is neuromodulation (Schofield & Hurley, 2018). The process of neuromodulation has been defined in different ways. Definitions are based on the identity and source of modulatory neurochemicals, the structure of synapses releasing neuromodulators, or the action of neuromodulatory receptors through second messenger systems (Maley et al., 1990; Marder, 2012; Nadim & Bucher, 2014). A useful functional perspective is based on a longstanding view of neuromodulators as reconfiguring the neural circuitry mediated by excitatory and inhibitory amino acid neurotransmitters like glutamate, GABA, and glycine. This chapter will focus on four types of neurochemicals that can fit one or more of these definitions: acetylcholine and the monoamines serotonin, norepinephrine, and dopamine. The effects of these neuromodulators in the auditory system follow basic principles that have been intensively studied for some time in motor systems (Marder, 2012), and are becoming more widely understood as an integral component of auditory processing (see Schofield & Beebe, this volume; Schofield & Hurley, 2018).

For the most part, this chapter will deal with neuromodulation by discrete groups of neurons that are extrinsic to the auditory system. It is important to note, however, that sources of neurochemical signals like acetylcholine and dopamine are also intrinsic components of auditory circuitry in the brainstem, which underlie feedback to early stages of auditory processing (Elgoyhen & Katz, 2012; Mulders & Robertson, 2004; Sherriff & Henderson, 1994). Auditory-extrinsic neuromodulatory centers show some striking functional similarities. One of these is their broad interaction with other neural sites. Neuromodulatory centers interconnect extensively with many other brain regions, including sensory, motor, and integrative sites (Benarroch, 2013; Lee et al., 2003; Luppi et al., 1995; Pollak Dorocic et al., 2014; Reese et al., 1995b; Retson & Van Bockstaele, 2013; Wang et al., 2006). These connections place neuromodulatory centers in position to instruct the auditory system on events in nonauditory brain regions.

All of the neuromodulatory regions discussed here also receive input from the auditory system, or possess populations of neurons that respond to acoustic stimuli (Aston-Jones & Bloom, 1981; Yasui et al., 1990; Reese et al., 1995a; Rasmussen et al., 1986; Heym et al., 1982). This reciprocity suggests that neuromodulatory systems could present a type of feedback to auditory neurons. A useful parallel model consists of descending pathways from the auditory cortex and IC, which are prominent features of auditory circuitry that provide feedback to the IC and auditory brainstem (e.g., Caicedo & Herbert, 1993); Schofield & Beebe, this volume). By virtue of their extensive connectivity with integrative brain regions that “interpret” external events, neuromodulatory systems could import information into the auditory system on situational variables that accompany acoustic stimuli, such as context, state, or salience (Petersen & Hurley, 2017).

The following sections present established and recent findings on neuromodulation in the IC and brainstem auditory nuclei in the framework of a feedback model. These sections emphasize major characteristics of auditory neuromodulation that are consistent with a feedback model, starting with the sources of neuromodulatory input, which originate in a diversity of neuron groups. In many cases, modulatory neurons are sensitive to acoustic stimuli, but represent “value-added” versions of these stimuli. The topography of terminal fields of neuromodulatory projections in the IC and brainstem auditory nuclei are specific and functionally suggestive. Once released from these projections, neuromodulatory signals within auditory regions encode information on behavioral salience. These neuromodulatory signals further multiplex information on external and internal events that occur on different time scales. Finally, neuromodulators functionally reconfigure auditory circuitry and alter behavioral responses to auditory stimulation.

Sources of Neuromodulatory Input to the IC and Auditory Brainstem

Ways to trace neuromodulatory sources

As prominent neuroanatomical features of the auditory system, neuromodulators in the IC and auditory brainstem have been studied for decades. Descriptions of modulatory projections to auditory brainstem nuclei based on histochemical reactions predate the use of selective labels for specific neurochemical pathways (Dahlstrom & Fuxe, 1964; Kromer & Moore, 1976; Levitt & Moore, 1979). The development of antibodies directed against specific monoamines, their synthetic enzymes, or selective transporters used in combination with tract tracing or selective neurotoxins has allowed for the sources of specific neuromodulatory inputs to the IC and many auditory brainstem nuclei to be identified (Hormigo et al., 2012; Klepper & Herbert, 1991; Motts & Schofield, 2009; Mulders & Robertson, 2005a). These studies portray a diverse set of neuromodulatory sources to the auditory system that in some cases have defied assumptions regarding their identity (Nevue et al., 2016a). This diversity is suggestive of a rich functional capability.

The extrinsic sources of neuromodulatory inputs to the IC and auditory brainstem have been extensively reviewed, for either single modulatory pathways (Schofield et al., 2011) or multiple pathways (Schofield & Hurley, 2018); this literature is therefore only briefly summarized here. Identifying modulatory sources typically involves retrograde or anterograde anatomical tracing, often accompanied by neurochemical identification of modulatory fibers or cell bodies (Klepper & Herbert, 1991; Motts & Schofield, 2009; Nevue et al., 2016a). Neurochemical identification has proven especially crucial, because most neuromodulatory nuclei house non-modulatory neurons that also project to the IC and auditory brainstem but use GABA or other neurotransmitters (Boucetta & Jones, 2009; Klepper & Herbert, 1991; Motts & Schofield, 2009; Nevue et al., 2016a; Vasudeva et al. 2011).

Where are auditory neuromodulators from?

There are multiple sources of cholinergic inputs to the IC and auditory brainstem nuclei. The cochlear nucleus receives inputs from cholinergic neurons in the auditory ventral nucleus of the trapezoid body, as well as tegmental cholinergic neurons in the pontomesencephalic tegmentum (Mellott et al., 2011). The IC itself receives projections from the pontomesencephalic cholinergic groups (Dautan et al., 2016; Motts & Schofield, 2009). An additional group of non-auditory cholinergic neurons projecting to the IC is found in the rostral ventrolateral medullary region (Stornetta et al., 2013). As a comparison, cholinergic innervation of the primary auditory cortex arises mainly from the basal forebrain (Bajo et al., 2014; Kamke et al., 2005). Thus, although many auditory sites receive cholinergic terminals, acetylcholine could be released under very different circumstances across auditory regions, depending on the source.

For other neuromodulatory pathways, the IC shares a dominant source with brainstem auditory nuclei. The IC and cochlear nucleus receive a majority of serotonergic projections from the dorsal raphe nucleus, with smaller although still substantial contributions from other raphe groups (Klepper & Herbert, 1991). The IC, cochlear nucleus, and superior olivary complex all receive noradrenergic input from the locus coeruleus (Klepper & Herbert, 1991; Mulders & Robertson, 2001). The understanding of dopaminergic innervation of the IC has changed with the addition of selective co-labels for the synthetic enzyme for dopamine. Although the dopaminergic substantia nigra projects to the IC (Olazábal & Moore, 1989), these projections may not be from dopaminergic neurons (Nevue et al., 2016a). Instead, some authors have suggested that the projections from substantia nigra to the IC are GABAergic (Maisonnette et al., 1996; Nobre et al., 2004). The IC and regions within the superior olivary complex receive dopaminergic projections from the subparafascicular nucleus (Nevue et al., 2016a, 2016b).

Hidden diversity within neuromodulatory sources

These findings together suggest that sources of cortical versus subcortical modulatory input are different for acetylcholine and dopamine, but similar for serotonin and norepinephrine. Even for seemingly universal modulatory sources like the dorsal raphe nucleus and locus coeruleus, however, there may be hidden variability, because these large modulatory centers are far from homogeneous (Calizo et al., 2011; Chandler et al., 2014a; Chandler et al., 2014b). In the dorsal raphe nucleus, subgroups of serotonergic neurons are distinguished by their position along rostrocaudal, mediolateral, and dorsoventral axes. Neurons in these different groups have afferent, efferent, and intrinsic distinctions (Calizo et al., 2011; Jacobs et al., 1978; Janusonis et al., 1999; Kirifides et al., 2001; Lee et al., 2003; Peyron et al., 1998; Van Bockstaele et al., 1993). For example, overlapping but distinct groups of dorsal raphe and locus coeruleus neurons project to cortical versus subcortical sensory sites (Kirifides et al., 2001; Waterhouse et al., 1993). In the locus coeruleus, subsets of noradrenergic neurons with distinct terminal fields show differential gene expression and electrophysiological characteristics (Chandler et al., 2014a).

Subpopulations of modulatory neurons may also be defined by their receptivity to other neurochemicals and their functional projections. For example, Pet1-positive dorsal raphe neurons expressing dopamine D2 receptors are involved in regulating aggressive behavior and project to a specific set of targets, sending strong projections to the IC and other auditory regions (Niederkofler et al., 2016). In general, although there is ample evidence that neuromodulatory centers have functionally distinct subsets of neurons, and of topographic organization of projections from neuromodulatory centers (Waterhouse et al., 1993; Waterhouse et al., 1986), the functional topographies of modulatory projections to the auditory system have not yet been well characterized.

Neuromodulatory Neurons Receive Auditory and Nonauditory Inputs

Auditory inputs

The connectivity and firing patterns of modulatory neurons provide one way of assessing the conditions that could trigger the release of neuromodulators within the auditory system. Consistent with a feedback model, all of the neuromodulatory regions relevant to this chapter either receive input from auditory regions (Figure 1), or respond to simple auditory stimuli like clicks and tones. Projections from different auditory regions to the pontomesencephalic tegmental nuclei or the subparafascicular nucleus have been well-documented (inferior colliculus: Wang et al., 2006; Yasui et al., 1990; medial geniculate body: LeDoux et al., 1985; auditory cortex: Schofield & Motts, 2009; Schofield, 2010; Yasui et al., 1990); some of these are described in detail in the chapter by Schofield and Beebe, in this volume. Pontomesencephalic tegmental neurons further show extremely short latency responses to clicks (< 10 ms) as well as longer-latency responses, although the auditory-responsive neurons have not been chemically identified (Reese et al., 1995a). Responses of neurons in the serotonergic dorsal raphe nucleus and noradrenergic locus coeruleus to auditory stimuli have been reported for decades (Aston-Jones & Bloom, 1981; Foote et al., 1980; Heym et al., 1982; Shima et al., 1986), and serotonergic dorsal raphe neurons receive monosynaptic inputs from the external subregion of the IC (Pollak Dorocic et al., 2014).

Neuromodulatory Feedback to the Inferior ColliculusClick to view larger

Figure 1. Evidence of anatomical connections between auditory and modulatory regions. A) Cell bodies labeled after placement of a retrograde tracer in the subparafascicular nucleus in rat. Subdivisions of the IC are labeled (LC = lateral cortex; CNIC = central nucleus of the IC; DC = dorsal cortex). (Adapted from Wang et al., 2006.) B) Fibers labeled by placement of an anterograde tracer in the magnocellular portion of the subparafascicular nucleus in rat. (Adapted from Yasui et al., 1992.) Note that projections are not neurochemically identified.

Nonauditory inputs

Auditory inputs constitute only a subset of the inputs into neuromodulatory nuclei, however. These nuclei typically receive extensive projections from a wide range of brain regions. The pontomesencephalic tegmental cholinergic nuclei are notably interconnected with motor control regions, as well as with hypothalamic regions involved in sleep/wake regulation (Benarroch, 2013). The subparafascicular nucleus, which contains dopaminergic neurons, is interconnected with regions that regulate reproductive behavior (Wang et al., 2006). The dorsal raphe nucleus and locus coeruleus likewise receive afferents from a wide range of brain regions representing many different functional domains, including areas important to cognitive function, social behavior, affective state, and stress (e.g., Lee et al., 2003; Luppi et al., 1995; Pollak Dorocic et al., 2014; Retson & Van Bockstaele, 2013).

Diverse inputs create integrative responses

Corresponding to this wide range of afferents, the auditory responsiveness of neurons in modulatory areas does not simply indicate the presence of auditory stimuli, but corresponds to additional factors such as internal state. Behavioral arousal is a state often associated with neuromodulators of all types. This includes arousal associated with phases of the sleep-wake cycle. The activity patterns of modulatory neurons are frequently tied to the sleep-wake cycle (Boucetta & Jones, 2009; Foote et al., 1980; Lorincz & Adamantidis, 2017; Motts & Schofield, 2009). Higher tonic firing rates typically occur during waking states, although firing rates may vary among modulatory systems during different sleep states. Internal states other than arousal are also represented within neuromodulatory axes, in that neuromodulatory activity depends on factors like social status and reproductive state (Challis et al., 2013; Hall et al., 2012; Hanson & Hurley, 2016; Korzan & Summers, 2007; Matragrano et al., 2012a; Matragrano et al., 2012b). Neuromodulatory systems may therefore not only modulate the tone of neural activity in sensory systems according to the level of behavioral arousal, but also promote optimal processing as it relates to specific internal states.

Across internal states, it is clear that neuromodulatory neurons integrate auditory and nonauditory sources of information about specific events. Modulatory neurons are often polysensory, responding to stimuli in multiple modalities (e.g., Aston-Jones & Bloom, 1981; Heym et al., 1982). Modulatory neurons also represent the salience of acoustic stimuli, a phenomenon that is well demonstrated by the responsiveness of modulatory neurons to reward contingencies. Extrinsic reward or the natural salience associated with acoustic stimuli affect the responses of neurons in multiple modulatory centers (Fischer & Ullsperger, 2017; Maney, 2013). In the locus coeruleus, for example, pairing tones with foot shock can create frequency-selective responses to tones alone even when tones do not initially evoke responses at all (Martins & Froemke, 2015). The responses of neuromodulatory neurons to acoustic stimuli therefore often represent the behavioral significance of these stimuli.

Neuromodulatory Inputs Broadly Innervate the IC and Auditory Brainstem

What does it mean to project diffusely?

Modulatory neurons are often described as projecting diffusely. This is true in the sense that modulatory fibers take apparently nondirect pathways through neural tissue and typically have many release sites along their length (Janusonis, 2017). These release sites may contain synaptic specializations, or be asynaptic. The latter configuration has been associated with the volume release of neuromodulators. In this mode, neuromodulators may diffuse some distance from their release sites before binding to receptors or transporters (Bunin & Wightman, 1998; Eid et al., 2013; Fuxe et al., 2015; but see Sarter et al., 2009 for a discussion of the controversy surrounding the concepts of volume versus synaptic transmission of acetylcholine). Although the synaptic configurations of neuromodulatory release sites have not been examined ultrastructurally in the IC, many serotonergic varicosities that form basket terminals around GABAergic neurons in the auditory cortex show only weak synaptic specializations (DeFelipe et al., 1991).

Neuromodulatory fiber patterns are selective

At the same time, modulatory fibers selectively innervate different subregions of the IC and auditory brainstem nuclei, or even specific layers, neural subgroups, or functionally distinct domains. On the broadest scale, some auditory brainstem nuclei seem to be relatively devoid of particular types of neuromodulatory inputs. For example, in the superior olivary complex of mice, the lateral superior olive does not receive dopaminergic innervation from the subparafascicular nucleus (Nevue et al., 2016b), and the guinea pig superior olivary complex as a whole receives few dopaminergic fibers (Mulders & Robertson, 2005a). The densities of serotonergic and noradrenergic fibers are generally higher in periolivary regions than in olivary nuclei themselves, although some fibers are present within olivary nuclei (e.g., Mulders & Robertson, 2005a; Thompson & Schofield, 2000; Wynne & Robertson, 1996). The MNTB shows a species-specific pattern of innervation by serotonergic fibers, which are present in bat but very scattered in mouse and cat (Hurley & Thompson, 2001; Thompson & Hurley, 2004; Thompson & Schofield, 2000).

In some species, neuromodulatory fiber densities correspond to tonotopic organization. Serotonergic fibers are denser in the regions corresponding to low-frequency responses than to high-frequency responses in the bat lateral and medial superior olives (Hurley & Thompson, 2001). Catecholaminergic fibers similarly are denser in the low-frequency regions of bat cochlear nucleus (Kössl et al., 1988). This pattern suggests that serotonin and norepinephrine or dopamine may modulate responses of low-frequency neurons more than high frequency neurons. Interestingly, although the same frequency-variable pattern of fibers is not observed in mice (Kössl et al., 1988; Thompson & Hurley, 2004), the mouse auditory brainstem response is generally more sensitive to serotonergic perturbation when stimuli consist of low-frequency tones compared to high-frequency tones, providing some functional support for frequency-selective modulatory effects (Papesh & Hurley, 2016).

Another type of pattern is for neuromodulatory inputs to be densest in integrative multimodal regions of auditory nuclei. Of the major subdivisions of the IC, serotonergic, noradrenergic, and dopaminergic fibers are denser in some pericentral subregions than in the central subdivision, although modulatory fibers are also clearly found within the central nucleus (Fyk-Kolodziej et al., 2015; Hormigo et al., 2012; Hurley & Thompson, 2001; Klepper & Herbert, 1991; Nevue et al. 2016a; Papesh and Hurley 2012; Figure 2). This pattern is also seen in the cochlear nucleus, in which the dorsal cochlear nucleus has denser serotonergic and catecholaminergic inputs than ventral subdivisions in some species (Klepper & Herbert, 1991; Kössl et al., 1988; Thompson & Thompson, 2001). These findings suggest that one role of multiple types of neuromodulators is to regulate the convergence of ascending auditory input with descending auditory input or nonauditory inputs (Hurley & Thompson, 2001; Klepper & Herbert, 1991). This hypothesis has received functional support in the case of serotonin, which alters the balance of auditory versus polysensory input at the level of fusiform neurons of the dorsal cochlear nucleus (Tang & Trussell, 2017).

Neuromodulatory Feedback to the Inferior ColliculusClick to view larger

Figure 2. Projections from neuromodulatory regions to the IC. A) Dense plexus of fibers labeled with an antibody to the serotonin transporter, which labels the projections of serotonergic neurons with high specificity. (Adapted from Keesom & Morningstar et al., 2018.) B) Locations of fibers (lines) and varicosities (circles) from virally labeled cholinergic fibers originating in the rostral ventrolateral medulla in mouse. Symbols represent the locations, but not the dimensions, of fibers and varicosities. Adapted from Stornetta et al. 2013. C) Fibers in the central subdivision of the IC labeled by placement of an anterograde tracer in the subparafascicular nucleus in mouse (green) and by an antibody to tyrosine hydroxylase (purple). Co-labeled fibers appear white. Arrow indicates fiber from the subparafascicular nucleus that is not catecholaminergic. (Adapted from Nevue et al., 2016a.)

Modulatory fibers even selectively innervate specific cellular layers or groups. In both the pericentral IC and the dorsal cochlear nucleus, noradrenergic fibers are sparsest in the outermost layer and denser in other layers, while serotonergic fibers show a reversed pattern; that is, are densest in the most external layer (Klepper & Herbert. 1991). These patterns are suggestive of layer-specific, complementary functions of different types of neuromodulators. Layer 2 of the lateral subregion of the IC exhibits a particularly intriguing structure of repeated neurochemical modules that co-localize acetylcholinesterase as well as cytochrome oxidase, NADPH, and glutamic acid decarboxylase (Chernock et al., 2004; Lesicko et al., 2016). Cholinergic inputs may therefore participate in a distinct neurochemical complex in these domains, which are the termination sites for somatosensory inputs (Lesicko et al., 2016). Specific neuron types also show selective anatomical targeting and functional effects of neuromodulation. In the ventral cochlear nucleus, T-stellate cells, but not D-stellate cells, are sensitive to cholinergic agonists (Fujino & Oertel, 2001). Olivocochlear neurons within the superior olivary complex are also particular targets of multiple types of neuromodulators including norepinephrine, serotonin, and peptide transmitters (Behrens et al., 2002; Mulders & Robertson, 2005a; 2000; Thompson & Schofield, 2000; Woods & Azeredo, 1999). Functionally, neurons in olivocochlear regions are responsive to application of norepinephrine and serotonin, with complementary effects on their descending targets (Mulders & Robertson, 2005b; Wang & Robertson, 1997).

All of these patterns are consistent with neuromodulatory systems targeting different kinds of anatomical domains. Although some evidence supports the functional hypotheses that arise from these patterns, these hypotheses have not been tested in many cases.

Neuromodulatory Activity in the IC and Auditory Brainstem

How is neuromodulatory activity in the auditory system measured?

The broad responsiveness of neurons within modulatory centers, combined with the prominent projections from these areas to auditory regions, creates the confusing potential for many different types of information to be imported into the auditory system. A way to resolve this ambiguity is to directly measure neuromodulatory activity under different behavioral circumstances. These types of measurements have been accomplished by microdialysis or localized tissue collection followed by HPLC measurement of neuromodulators and their major metabolites (Cransac et al., 1998; Matragrano et al., 2012b). Additionally, antibodies specific for activated forms of modulatory synthetic enzymes, or carbon fiber voltammetry, can capture neuromodulatory activity (Hall et al., 2010; Matragrano et al., 2012a). Most of the studies in this area have assessed either serotonergic or noradrenergic activity on relatively broad spatial and temporal scales rather than on the scale of synaptic events.

Acoustic and nonacoustic stimuli influence neuromodulatory activity

Absolute changes in the levels of serotonin and norepinephrine and their major metabolites have been measured following exposure to noise in the cochlear nucleus, IC, and auditory cortex. These show activation of modulatory pathways that is specific to particular auditory nuclei and their subregions, and that varies with sound level. For example, noise alters the ratios of serotonin and norepinephrine relative to their metabolites in tissue containing both the dorsal and posteroventral cochlear nuclei, but not in the anteroventral cochlear nucleus (Cransac et al., 1998). These ratios are generally interpreted as an indication of modulatory release and subsequent metabolism, termed “turnover.” Modulatory turnover is dependent on the intensity of noise; noradrenergic turnover in the cochlear nucleus and serotonergic turnover in the auditory cortex are only seen at relatively low intensities. Voltammetric measurements suggest that serotonergic activity increases modestly in the IC with moderate noise levels (Hall et al., 2010). In neither of these studies was the relationship of noise exposure to levels of systemic stress explored. However, nonauditory stressors including confinement to a small arena also increase serotonergic activity in the IC (Hall et al., 2010; Hall et al., 2012; Hanson & Hurley, 2014). Glucocorticoids do not directly evoke this release, since the systemic injection of corticosterone has no effect on serotonergic activity (Hall et al., 2012). Not all purported inducers of stress influence auditory serotonin, however. The presentation of an olfactory stressor, a chemical component of fox urine that induces strong aversive responses in mice, does not significantly alter serotonergic activity in the IC (Hall et al., 2010). Thus, increases in neuromodulatory activity in the IC in response to simple stimuli, even stimuli that share threatening qualities, are quite selective.

Neuromodulatory activity during social interaction

A more complex context that increases serotonergic activity in the IC is presentation of a social partner. Serotonergic increases occur across a range of different types of encounters: in males interacting with males or with females (Hall et al., 2011; Hurley & Hall, 2011; Keesom & Hurley, 2016) and in females interacting with males (Hanson & Hurley, 2014). Within each of these types of encounters, across-individual variation in serotonergic activity corresponds to variation in behavior. In male-male interactions, for example, serotonergic activity correlates with social investigation by the experimental subjects, and with overall movement (Hall et al., 2011). Males that are more active and more socially investigative show the largest serotonergic increases. In contrast, serotonergic activity in males interacting with females correlates inversely with the rejection behaviors of the female partners, but not with behaviors of the subject males (Keesom & Hurley, 2016). Individual males that experience the most rejection, including female-produced broadband vocalizations (“squeaks”), do not show serotonergic increases. In this case, serotonin levels inversely correspond to a specific type of auditory stimulus (female-produced squeaks) and are more representative of the valence, or positive versus negative behavioral value, of the situation for individual males.

Internal state and experience play a role

Serotonergic pathways within the IC are also capable of multiplexing information about behaviorally relevant events that occur on different timescales. This is accomplished through plasticity at different levels of the serotonergic system. For example, internal state is one factor that is encoded by serotonin release. Serotonergic activity in the IC increases as animals recover from anesthesia (Hall et al., 2010). This may be due to increased firing rates of neurons in the dorsal raphe nucleus (Sakai & Crochet, 2001). Reproductive cycles may also induce long-term changes in the infrastructure of serotonin in the auditory midbrain. Implanting female white-throated sparrows with estradiol, which would normally increase during their breeding season, augments the density of serotonergic fibers in an avian auditory midbrain nucleus that is a homolog of the IC (Matragrano et al., 2012b). In a parallel study in males, treatment with testosterone to mimic breeding levels results in a decrease in both serotonergic and noradrenergic fibers in the auditory midbrain (Matragrano et al., 2013). Seasonally breeding fish also experience neuromodulatory plasticity in both the auditory periphery and central auditory system (Forlano & Sisneros, 2016). Reproductively related changes in neuromodulation are not limited to seasonally reproducing animals. In female lab mice, the effects of manipulating serotonin levels on immediate early gene activity in the IC depends on the naturally cycling estrous phase (Hanson & Hurley, 2016). This result suggests change at the level of responsiveness to serotonin release, potentially in the expression of serotonin receptors by IC neurons. Neuromodulatory systems are therefore regulated at times when acoustic social signals have particular significance for reproduction.

Experience of multiple kinds also alters serotonergic infrastructure. Monaural acoustic trauma alters the bilateral balance of serotonergic fibers in the IC, decreasing fibers in the IC contralateral to trauma relative to the ipsilateral side (Papesh & Hurley, 2012). Bilateral cochlear ablation likewise decreases the density of fibers immunoreactive for tyrosine hydroxylase, a synthetic enzyme for dopamine and norepinephrine (Tong et al., 2005). Binaural acoustic trauma or ablation, as well as age-associated hearing loss, upregulate or downregulate the expression of several types of serotonin receptors in the IC relative to controls (Holt et al., 2005; Smith et al., 2014; Tadros et al., 2007). This includes at least one type of receptor that is expressed strongly in the IC as measured both immunohistochemically and by ligand binding studies, the 5-HT1A receptor (Peruzzi & Dut, 2004; Smith et al., 2014; Thompson et al., 1994). This evidence suggests that serotonin receptor expression by auditory neurons is altered following hearing loss. The effects of acoustic trauma and hearing loss on modulatory systems therefore occur at levels that are both presynaptic and postsynaptic to modulatory fibers within the IC.

Postweaning social isolation is another class of experience that alters serotonergic activity in the IC (Keesom et al., 2017). Male mice housed in same-sex social groups versus in isolation for a period of weeks after the time of weaning show two key differences when acutely challenged with an unfamiliar social partner. Individually housed mice have more sluggish serotonergic responses that peak later than those of socially housed mice, although their relative amplitudes do not differ. Individually housed mice also do not exhibit the correlations between serotonergic activity and behavior that are typical for socially housed mice (Hall et al., 2011; Keesom et al., 2017). Thus, serotonin release may be dysregulated relative to variation in the social context for mice with less social experience.

Together, these types of studies illustrate that neuromodulatory activity in auditory regions does not faithfully represent acoustic stimuli, but instead may encode the value of particular situations, internal state, and different kinds of experience. These factors may be represented at multiple levels of modulatory systems, including in the level of modulatory release and responsiveness, and in neuromodulatory infrastructure including the density of fibers and receptor expression (Figure 3)

Neuromodulatory Feedback to the Inferior ColliculusClick to view larger

Figure 3. External events, internal state, and experience alter the serotonergic modulatory system within the IC at multiple levels. Schematic representation of serotonergic projections from the dorsal raphe nucleus to the IC. Behaviorally relevant variables alter serotonergic fiber density (orange line), serotonin availability (asterisks), and the expression of serotonin receptors (purple and green shapes) by IC neurons.

Neuromodulators Functionally Reconfigure Auditory Circuitry

Once released in the IC and auditory brainstem, neuromodulators have profound effects; all four neurochemicals discussed in this chapter influence the firing patterns or response properties of substantial proportions of IC neurons. These effects fit a classic model of neuromodulators as reconfiguring neural circuitry by targeting specific aspects of cellular function (Harris-Warrick & Johnson, 2010; Marder & Bucher, 2007).

Receptors determine modulatory effects

The effects of neuromodulatory release on the intrinsic properties and sound-evoked responses of auditory neurons depend upon the types of receptors expressed by target neurons (Hurley & Sullivan, 2012). For example, many neuromodulators have suppressive effects on neural firing for some IC neurons, and facilitatory effects for others (e.g., acetylcholine: Habbicht & Vater, 1996; serotonin: Hurley & Pollak, 1999; dopamine: Gittelman et al., 2013). In some cases, these differences are positively attributable to the activation of different receptor types. For acetylcholine, a nicotinic antagonist increases neural activity while a broad-spectrum muscarinic antagonist generally decreases activity (Habbicht & Vater, 1996). There is further diversity even among muscarinic receptor subtypes, since m1 and m2 muscarinic acetylcholine receptor antagonists have different effects. For serotonin, selective agents for receptors in at least three of the seven receptor families have characteristic suppressive or facilitatory physiological effects on sound-evoked responses (Bohorquez & Hurley, 2009; Hurley, 2007, 2006). This general phenomenon of multiple types of effects of single neuromodulators is widespread, and is also observed in a number of auditory brainstem nuclei (e.g., Ebert, 1996; Ebert & Ostwald, 1992; Kössl & Vater, 1989; Wang & Robertson, 1997). Rather than canceling each other out, such opposing effects may result in greater selectivity for specific inputs at the level of auditory microcircuitry, may shape temporal responses, or may stabilize new circuit configurations (Harris-Warrick & Johnson, 2010; Kössl & Vater, 1989; Tang & Trussell, 2017).

Neural phenotypes influence modulatory effects

The effects of neuromodulators also depend on the identities of neurons expressing the relevant receptors. Given the importance of inhibitory inputs in the IC to the response properties of IC neurons (Pollak, 2013; Pollak et al., 2002; Pollak et al., 2011), neuromodulation of inhibition has been a particular focus for some studies. There is robust evidence for modulation of GABAergic and glycinergic inputs to IC neurons by both acetylcholine and serotonin. In slice preparations, activation of muscarinic receptors or 5-HT2 receptors creates a dramatic increase in the frequency of spontaneous GABAergic inhibitory postsynaptic currents, and a 5-HT2 agonist also increases their amplitude (Wang et al., 2008; Yigit et al., 2003). Serotonin also increases the frequency of glycinergic postsynaptic currents, although not as dramatically (Obara et al., 2014). Because some of these effects can be prevented by blocking action potentials with tetrodotoxin, these increases in inhibitory activity are thought to represent enhanced spontaneous firing of presynaptic inhibitory neurons. It is not clear whether these effects are limited to a specific developmental phase, as are similar effects of serotonin in the lateral superior olive (Fitzgerald & Sanes, 1999).

The 5-HT1B receptor may also act through inhibitory neurons. This receptor increases sound-evoked activity of many IC neurons (Baldan Ramsey et al., 2010; Hurley, 2006; Hurley et al., 2008). In other brain regions, the 5-HT1B receptor generally acts by limiting synaptic transmission, and its effects in the IC are reduced in the presence of a GABAA receptor agonist, consistent with effects of the 5-HT1B receptor on presynaptic GABAergic neurons (Hurley et al., 2008; Sari, 2004). Likewise, although the D2 receptor is the predominant dopamine receptor type in the IC, dopamine application to the IC has heterogeneous effects, potentially by influencing presynaptic GABAergic neurons (Gittelman et al., 2013). Although inhibition is clearly an important functional target of neuromodulation in the IC, neuromodulators likely influence the activity of non-GABAergic neurons too (Hurley & Sullivan, 2012; Peruzzi & Dut, 2004).

Subcellular targets

Neuromodulators selectively target specific subcellular compartments; this type of selectivity has been most thoroughly explored in different auditory brainstem nuclei. At the Calyx of Held, both norepinephrine acting via α2 adrenergic receptors and serotonin acting via 5-HT1B receptors limit calcium influx presynaptically at early developmental stages, resulting in reduced release of glutamate (Leão & Von Gersdorff, 2002; Mizutani et al., 2006). Neuromodulators can also alter intrinsic excitability by changing the membrane potential (Goyer et al., 2016; Miko & Sanes, 2009). Further, neuromodulators selectively alter neural output. For cartwheel cells in the dorsal cochlear nucleus, dopaminergic D3 receptors shift firing patterns from a bursting to a regular-firing mode by decreasing T-type calcium current selectively in the axon initial segment (Bender et al., 2010, 2012). For MSO neurons, activation of 5-HT1A receptors hyperpolarizes the membrane potential in the axon initial segment and decreases spike threshold (Ko et al., 2016). These selective effects occur partly through targeting particular types of ion currents. For example, the activation curve of the hyperpolarization-activated, cyclic nucleotide- gated cation current is shifted by norepinephrine in the MNTB and the avian nucleus laminaris (Banks et al., 1993; Yamada et al., 2005), and by serotonin in the MSO and DCN (Ko et al., 2016; Tang & Trussell, 2015).

Functional outcomes of targeted effects

In the IC, this range of selective modulatory mechanisms results in the transformation of functional response properties. Neuromodulators commonly alter the spontaneous or evoked firing rates of IC neurons in response to stimuli (Curtis & Koizumi, 1961; Gittelman et al., 2013; Hurley et al., 2004; Hurley & Pollak, 1999). Neuromodulators also alter firing patterns (Gittelman et al., 2013; Habbicht & Vater, 1996), latency or latency jitter (Felix et al., 2017; Gittelman et al., 2013; Hurley, 2007; Hurley & Pollak, 2005b), or selectively alter frequency tuning (Hurley & Pollak, 2001). These types of changes can contribute to shifts in neural selectivity for spectrotemporally divergent sounds, such as tones versus FM sweeps (Hurley & Pollak, 1999), sounds of different frequency (Hurley et al., 2004; Hurley & Pollak, 2001) or different species-specific vocalizations (Hurley & Pollak, 2005a).

Responses of IC neurons to temporally complex stimuli are also altered by neuromodulation. Ionotropic 5-HT3 receptors are responsible for a seconds-long depolarization of a few millivolts in baseline membrane potential following stimulus barrage to lemniscal inputs. This depolarization increases the gain of the neural response to a single stimulus of the input fibers (Miko & Sanes, 2009). In vivo, the same receptor type causes responses to different acoustic stimulus rates to become more similar (Bohorquez & Hurley, 2009). For neurons that show stimulus-specific adaptation, acetylcholine equalizes responses between rare and common stimuli by decreasing adaptation to the common stimulus (Ayala & Malmierca, 2015; Ayala et al., 2016). These types of effects demonstrate that neuromodulators regulate the responses to local auditory context.

A superb example of how neuromodulatory effects at the level of multiple auditory neurons within a microcircuit combine to create functionally coherent change is seen for the effects of serotonin in the dorsal cochlear nucleus. Serotonin acts through multiple receptor types and multiple cell types converging on fusiform cells to enhance multisensory responses and dampen auditory-only responses (Tang & Trussell, 2017, 2015). These types of combinatorial processes also occur in the IC. For example, 5-HT1A and 5-HT1B receptors both influence the responses of high proportions of neurons, but in opposite ways. Activation of 5-HT1A receptors often reduces responses to acoustic stimuli and delays spikes, consistent with suppression of excitability in other brain regions by this receptor (Hurley, 2007; 2006; Ohno, 2010). In contrast, 5-HT1B activation usually increases the responses of IC neurons to acoustic stimuli, consistent with a presynaptic reduction of GABAergic transmission (Hurley et al., 2008; Sari, 2004). Some IC neurons respond to activation of both of these types of receptors (Baldan Ramsey et al., 2010). For these double-responsive neurons, the effects of activating both receptor types on spike rate is linear, in that large effects of a given receptor type alone correspond to large effects when applied in combination. However, effects on spike latency are dominated by the 5-HT1A receptor. Thus, different types of neuromodulatory receptor may combine in nonlinear ways to create distinct profiles of neural activity.

Neuromodulators do not act alone

Creating additional potential for complex regulatory effects, different neuromodulatory systems also interact with each other. In some auditory regions, neuromodulatory systems are activated during some of the same events, including associative training (dopamine and serotonin: Stark & Scheich, 1997) or exposure to noise (norepinephrine and serotonin: Cransac et al., 1998; Hall et al., 2010). In each of these cases, although multiple neuromodulators are activated in the same general stimulus paradigm, the patterns of neuromodulatory release across stimulus conditions or across auditory regions are distinct. Profiles of release across different neuromodulators could therefore be more informative than for any single neuromodulator. At the level of auditory neurons and the receptors that they express, specific neuron types in the auditory brainstem and midbrain are the targets of multiple neuromodulatory systems (e.g., cartwheel cells: (Bender et al., 2010; He et al., 2014; Kuo & Trussell, 2011), calyx of Held: (Leão & Von Gersdorff, 2002; Mizutani et al., 2006). A very few studies have also documented responsiveness of the same individual auditory neurons to multiple types of neuromodulators (Hurley et al., 2004; McCormick & Pape, 1990). Different neuromodulatory systems therefore are likely to collaborate in their influence on auditory circuitry.

Behavioral Functions of Neuromodulation in in the IC

Building and testing hypotheses for the perceptual outcomes of auditory neuromodulation requires reconciling the exceptional breadth of neuromodulatory capabilities with specific behavioral contexts and auditory circuits (Linster & Cleland, 2016). A well-explored and well-reviewed example of the influence of neuromodulators on auditory perception is plasticity in responses to the pairing of tones with aversive stimuli like shock. Multiple types of neuromodulators, including acetylcholine, dopamine, and norepinephrine, alter the representation of frequency in auditory cortex and may change behavior following associative learning in parallel (Bao et al., 2001; Martins & Froemke, 2015; Weinberger, 2015). In the auditory cortex, local modulation with a peptide neurotransmitter, oxytocin, also alters neural responses in step with maternal responses to pup calls (Marlin et al., 2015).

Neuromodulatory regulation of aversion

Through effects in the IC, neuromodulation influences several classes of behaviors. These include unconditioned and conditioned aversion. Electrical or chemical stimulation of the central subdivision of the IC induces a variety of unconditioned fearful or aversive behaviors, including arousal, freezing, and escape behaviors (Brandão et al., 1994; Brandão et al., 1999). IC stimulation can even serve as an unconditioned aversive stimulus in operant conditioning paradigms in which animals leave a chamber to discontinue the stimulus (Melo & Brandão, 1995). These findings have led to a model of the IC as part of a mesencephalic substrate for defensive behaviors, along with regions of the periaqueductal gray and superior colliculus (Brandão et al., 1999). Local injection of neuromodulators or their specific receptor agonists or antagonists into the IC can modify these defensive behaviors. Zimelidine, a serotonin reuptake inhibitor, reduces the number and increases the latency of conditioned aversive behaviors when it is injected into the IC (Brandão et al., 1993; Melo and Brandão 1995). Injection of 5-HT1A or 5-HT2A agonists have similar effects, consistent with the prevalence of each of these receptor types in the IC (Melo & Brandão, 1995; Peruzzi & Dut, 2004; Smith et al., 2014; Thompson et al., 1994; Wang et al., 2008). Injection of sulpiride, a D2 dopaminergic receptor antagonist, into the IC increases avoidance of open arms in the elevated plus maze as well as the amplitude of the auditory evoked potential recorded locally in the IC (de Oliveira et al., 2014). Thus, multiple neuromodulatory systems dampen aversive behavioral responses to stimulation of the IC.

Neuromodulatory regulation of prepulse inhibition

Auditory prepulse inhibition is another phenomenon in which the IC plays an important role (Gomez-Nieto et al., 2008; Li & Yue, 2002; Yeomans et al., 2006). The startle response to an acoustic stimulus can be reduced by a non-startling transient prepulse or by electrical stimulation of the IC, and is also disrupted by lesion of the IC (Leitner & Cohen, 1985; Li et al., 1998a; Li et al., 1998b). This suppression may protect the response to the initial sound (prepulse), and involves specific subcortical circuitry in which the IC contributes information about the prepulse (Carlson & Willott, 1998; Fendt et al., 2001; Leitner & Cohen, 1985; Li & Yue, 2002). Cholinergic pathways originating in the pontomesencephalic tegmentum are also important to this circuit (Fendt et al., 2001; Koch et al., 1993). Consistent with this model, local effects of neuromodulators in the IC alter prepulse inhibition. Unilateral injection of 2,5-Dimethoxy-4-iodoamphetamine, an agonist of 5-HT2 receptors, reduces prepulse inhibition but does not affect the amplitude of the acoustic startle response itself (de Oliveira et al., 2017). The injection of D2 agonists into the IC induces similar effects (Satake et al., 2012).

All together, these findings show that in addition to being a site for the modulation of ascending auditory information, the IC is involved in subcortical circuitry that modifies responses to potentially threatening stimuli. Multiple types of neuromodulators can influence these defensive behaviors through local effects within the IC.

Do Neuromodulatory Systems Really Provide Feedback to Auditory Circuits?

The previous sections illustrate that auditory and modulatory regions are anatomically interconnected. Despite this evidence, it would not be an accurate reflection of a broad body of literature to say that neuromodulatory systems simply channel instructive feedback to the auditory system. One reason for this is that modulatory systems are both downstream and upstream of integrative brain regions such as the prefrontal cortex, amygdala, hypothalamic nuclei, or bed nucleus of the stria terminalis (Benarroch, 2013; Lee et al., 2003; Luppi et al., 1995; Mena-Segovia & Bolam, 2017; Parent et al., 1981; Pollak Dorocic et al., 2014; Retson & Van Bockstaele, 2013). Modulatory systems may therefore play an important role in establishing, as well as distributing, information regarding stimulus salience.

A second way that neuromodulatory systems violate a linear model of auditory feedback circuitry is illustrated by a widely expressed anatomical feature of modulatory neurons: they often send collateral projections to divergent targets. These collaterals can potentially couple modulatory signals in different auditory regions. Dopaminergic neurons in the subparafascicular nucleus, cholinergic neurons in the pedunculopontine tegmental nucleus, and noradrenergic neurons in the locus coeruleus all send collaterals to multiple auditory targets (Klepper & Herbert, 1991; Nevue et al., 2016b; Schofield et al., 2011). As might be expected from this pattern of projections, the effects of neuromodulators at different levels interact. For example, acetylcholine applied locally to the IC influences auditory cortical plasticity, and vice versa (Ma & Suga, 2005). Many collaterals of modulatory neurons are even more divergently projecting, targeting not only sensory regions, but non-sensory regions too (e.g., Lee et al., 2009; Villar et al., 1988). This pattern could result in neuromodulatory release under the same conditions in functionally divergent brain regions. As an example, serotonin levels in both the IC and the preoptic area increase when male rodents interact with females, and depend on the females being sexually available (Fumero et al., 1994; Keesom & Hurley, 2016; Mas et al., 1995). Neuromodulatory systems are therefore capable of broadly coordinating neural activity across sensory, motor, and motivational systems.

Interactions among the IC, amygdala, and modulatory systems

The functional entanglement that arises from these types of interactions is highlighted by a series of studies illustrating the modulatory control of unconditioned aversive behavior evoked by stimulation of the IC. As described earlier, electrical stimulation of the IC evokes aversive behavior, and local injection of serotonergic and dopaminergic agents into the IC dampen some of these aversive behavioral responses. The amygdala is another site that regulates aversive behaviors and that interacts with the IC, in which neuromodulators influence behavioral output. Lesion of the central amygdala increases aversive thresholds to stimulation of the IC but lesion of the basolateral amygdala decreases them (Maisonnette et al., 1996). This finding is consistent with a model of the amygdala as downstream of the IC in the regulation of aversive behaviors. Modulatory nuclei may also act as functional intermediaries between the IC and amygdala, in that stimulation of the IC causes increased release of serotonin and dopamine within the basolateral amygdala, although less in the central amygdala (Macedo et al., 2005). The actions of serotonin and dopamine in the amygdala exert complex effects on defensive behavior. The local injection of serotonergic and dopaminergic antagonists within the basolateral amygdala dampens conditioned place aversion but enhances unconditioned aversion in response to chemical stimulation of the IC (Macedo et al., 2007). Likewise, selective neurochemical lesion of serotonergic fibers in the central amygdala increases thresholds for alertness, freezing, and escape behavior caused by IC stimulation, while neurochemical lesion within the basolateral complex decreases thresholds for these behaviors (Macedo et al., 2002). Finally, anatomical pathways from the amygdala to the IC suggest an additional route for direct amygdalo-collicular feedback (Marsh et al., 2002). Functionally, manipulation of inhibitory neurotransmission in the amygdala alters the amplitude of locally measured auditory evoked potentials in the IC (Nobre & Brandão, 2011). Arising from these somewhat complicated results is an important general point. It is not simply the case that the auditory system and neuromodulatory systems mutually influence each another, a point made at length in this chapter. Rather, recursive connections among auditory, interpretive, and modulatory systems all interact to regulate behavior (Figure 4)

Neuromodulatory Feedback to the Inferior ColliculusClick to view larger

Figure 4. Schematic diagram illustrating some of the connections among auditory, modulatory, and other brain regions. Feedback loop between auditory and modulatory regions is emphasized by solid orange outlines and arrows. ACh = acetylcholine; 5-HT = serotonin; NE = norepinephrine; DA = dopamine; glut = glutamate; PMT = pontomesencephalic tegmentum; SPF = subparafascicular nucleus; LC = locus coeruleus; DRN = dorsal raphe nucleus.

Conclusion: Neuromodulators Are a Substrate for Auditory and Nonauditory IntegrationUnderstanding the actions of neuromodulatory pathways in the auditory system requires thinking about the auditory system from its earliest levels as anatomically and functionally interwoven with non-auditory regions of the brain. Neuromodulatory systems channel integrative information to the auditory system, providing the potential for auditory circuits to adjust their activity to conform to salient events, internal state, or experience. Auditory neuromodulation influences behavioral responses to sound, but the importance of modulatory pathways to behavior depends on the circuitry underlying specific behavioral tasks, the functional connectivity between modulatory subgroups and auditory regions, and the behavioral context. A circuit-based approach will therefore be crucial to better understanding auditory neuromodulation and the roles that modulatory processes play in perception and behavior.

The extensive interactions between auditory and modulatory regions also potentially give auditory neurons the power to mediate the transformation between external events and internal representations such as valence or salience (Petersen & Hurley, 2017). In part through the influence of modulatory systems, auditory neurons may be active participants in extracting information relevant to specific contexts, states, or histories of individuals, and consequently have a profound influence on behavioral output. Ultimately, mutual influence by auditory and interpretive systems may optimally shape behavior to best match the dynamics of an animal’s internal and external environments.


Aston-Jones, G., & Bloom, F. E. (1981). Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. Journal of Neuroscience, 1(8), 887–900.Find this resource:

Ayala, Y. A., & Malmierca, M. S. (2015). Cholinergic modulation of stimulus-specific adaptation in the inferior colliculus. Journal of Neuroscience, 35(35), 12261–12272. doi:10.1523/JNEUROSCI.0909-15.2015Find this resource:

Ayala, Y. A., Perez-Gonzalez, D., & Malmierca, M. S. (2016). Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs. Biological Psychology, 116, 10–22. doi:10.1016/j.biopsycho.2015.06.016Find this resource:

Bajo, V. M., & King, A. J. (2012). Cortical modulation of auditory processing in the midbrain. Frontiers in Neural Circuits, 6, 114. doi:10.3389/fncir.2012.00114Find this resource:

Bajo, V. M., Leach, N. D., Cordery, P. M., Nodal, F. R., & King, A. J. (2014). The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex. European Journal of Neuroscience, 40(6), 2922–2940. doi:10.1111/ejn.12653Find this resource:

Baldan Ramsey, L. C., Sinha, S. R., & Hurley, L. M. (2010). 5-HT1A and 5-HT1B receptors differentially modulate rate and timing of auditory responses in the mouse inferior colliculus. European Journal of Neuroscience, 32(3), 368–379. doi:10.1111/j.1460-9568.2010.07299.xFind this resource:

Banks, M. I., Pearce, R. A., & Smith, P. H. (1993). Hyperpolarization-activated cation current (Ih) in neurons of the medial nucleus of the trapezoid body: Voltage-clamp analysis and enhancement by norepinephrine and cAMP suggest a modulatory mechanism in the auditory brain stem. Journal of Neurophysiology, 70(4), 1420–1432. doi:10.1152/jn.1993.70.4.1420Find this resource:

Bao, S., Chan, V. T., & Merzenich, M. M. (2001). Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature, 412(6842), 79–83. doi:10.1038/35083586Find this resource:

Bartlett, E. L. (2013). The organization and physiology of the auditory thalamus and its role in processing acoustic features important for speech perception. Brain and Language, 126(1), 29–48. doi:10.1016/j.bandl.2013.03.003Find this resource:

Behrens, E. G., Schofield, B. R., & Thompson, A. M. (2002). Aminergic projections to cochlear nucleus via descending auditory pathways. Brain Research, 955(1–2), 34–44.Find this resource:

Benarroch, E. E. (2013). Pedunculopontine nucleus: Functional organization and clinical implications. Neurology, 80(12), 1148–1155. doi:10.1212/WNL.0b013e3182886a76Find this resource:

Bender, K. J., Ford, C. P., & Trussell, L. O. (2010). Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation. Neuron, 68(3), 500–511. doi:10.1016/j.neuron.2010.09.026Find this resource:

Bender, K. J., Uebele, V. N., Renger, J. J., & Trussell, L. O. (2012). Control of firing patterns through modulation of axon initial segment T-type calcium channels. Journal of Physiology, 590(1), 109–118. doi:10.1113/jphysiol.2011.218768Find this resource:

Bohorquez, A., & Hurley, L. M. (2009). Activation of serotonin 3 receptors changes in vivo auditory responses in the mouse inferior colliculus. Hearing Research, 251(1–2), 29–38. doi:10.1016/j.heares.2009.02.006Find this resource:

Boucetta, S., & Jones, B. E. (2009). Activity profiles of cholinergic and intermingled GABAergic and putative glutamatergic neurons in the pontomesencephalic tegmentum of urethane-anesthetized rats. Journal of Neuroscience, 29(14), 4664–4674. doi:10.1523/JNEUROSCI.5502-08.2009Find this resource:

Brandão, M. L., Anseloni, V. Z., Pandóssio, J. E., De Araújo, J. E., & Castilho, V. M. (1999). Neurochemical mechanisms of the defensive behavior in the dorsal midbrain. Neuroscience and Biobehavioral Reviews, 23(6), 863–875.Find this resource:

Brandão, M. L., Cardoso, S. H., Melo, L. L., Motta, V., & Coimbra, N. C. (1994). Neural substrate of defensive behavior in the midbrain tectum. Neuroscience and Biobehavior Reviews, 18(3), 339–346.Find this resource:

Brandão, M. L., Melo, L. L., & Cardoso, S. H. (1993). Mechanisms of defense in the inferior colliculus. Behavioural Brain Research, 58(1–2), 49–55.Find this resource:

Bulkin, D. A., & Groh, J. M. (2012). Distribution of visual and saccade related information in the monkey inferior colliculus. Frontiers in Neural Circuits, 6, 61. doi:10.3389/fncir.2012.00061Find this resource:

Bunin, M. A., & Wightman, R. M. (1998). Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: an investigation of extrasynaptic transmission. Journal of Neuroscience, 18(13), 4854–4860.Find this resource:

Caicedo, A., & Herbert, H. (1993). Topography of descending projections from the inferior colliculus to auditory brainstem nuclei in the rat. Journal of Comparative Neurology, 328(3), 377–392. doi:10.1002/cne.903280305Find this resource:

Calizo, L. H., Akanwa, A., Ma, X., Pan, Y. Z., Lemos, J. C., Craige, C., … Beck, S. G. (2011). Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence. Neuropharmacology, 61(3), 524–543. doi:10.1016/j.neuropharm.2011.04.008Find this resource:

Carlson, S., & Willott, J. F. (1998). Caudal pontine reticular formation of C57BL/6J mice: responses to startle stimuli, inhibition by tones, and plasticity. Journal of Neurophysiology, 79(5), 2603–2614. doi:10.1152/jn.1998.79.5.2603Find this resource:

Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., … Berton, O. (2013). Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. Journal of Neuroscience, 33(35), 13978–13988, 13988a. doi:10.1523/JNEUROSCI.2383-13.2013Find this resource:

Chandler, D. J., Gao, W. J., & Waterhouse, B. D. (2014a). Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices. Proceedings of the National Academy of Sciences of the United States of America, 111(18), 6816–6821. doi:10.1073/pnas.1320827111Find this resource:

Chandler, D. J., Waterhouse, B. D., & Gao, W. J. (2014b). New perspectives on catecholaminergic regulation of executive circuits: evidence for independent modulation of prefrontal functions by midbrain dopaminergic and noradrenergic neurons. Frontiers in Neural Circuits, 8, 53. doi:10.3389/fncir.2014.00053Find this resource:

Charitidi, K., & Canlon, B. (2010). Estrogen receptors in the central auditory system of male and female mice. Neuroscience, 165(3), 923–933. doi:10.1016/j.neuroscience.2009.11.020Find this resource:

Chernock, M. L., Larue, D. T., & Winer, J. A. (2004). A periodic network of neurochemical modules in the inferior colliculus. Hearing Research, 188(1–2), 12–20. doi:10.1016/S0378-5955(03)00340-XFind this resource:

Choy Buentello, D., Bishop, D. C., & Oliver, D. L. (2015). Differential distribution of GABA and glycine terminals in the inferior colliculus of rat and mouse. Journal of Comparative Neurology, 523(18), 2683–2697. doi:10.1002/cne.23810Find this resource:

Coomes, D. L., & Schofield, B. R. (2004). Separate projections from the inferior colliculus to the cochlear nucleus and thalamus in guinea pigs. Hearing Research, 191(1–2), 67–78. doi:10.1016/j.heares.2004.01.009Find this resource:

Cransac, H., Cottet-Emard, J. M., Hellstrom, S., & Peyrin, L. (1998). Specific sound-induced noradrenergic and serotonergic activation in central auditory structures. Hearing Research, 118(1–2), 151–156.Find this resource:

Curtis, D. R., & Koizumi, K. (1961). Chemical transmitter substances in brain stem of cat. Journal of Neurophysiology, 24, 80–90. doi:10.1152/jn.1961.24.1.80Find this resource:

Dahlstrom, A., & Fuxe, K. (1964). Localization of monoamines in the lower brain stem. Experientia, 20(7), 398–399.Find this resource:

Dautan, D., Hacioglu Bay, H., Bolam, J. P., Gerdjikov, T. V., & Mena-Segovia, J. (2016). Extrinsic sources of cholinergic innervation of the striatal complex: A whole-brain mapping analysis. Frontiers in Neuroanatomy, 10, 1. doi:10.3389/fnana.2016.00001Find this resource:

DeFelipe, J., Hendry, S. H., Hashikawa, T., & Jones, E. G. (1991). Synaptic relationships of serotonin-immunoreactive terminal baskets on GABA neurons in the cat auditory cortex. Cerebral Cortex, 1(2), 117–133.Find this resource:

de Oliveira, A. R., Colombo, A. C., Muthuraju, S., Almada, R. C., & Brandao, M. L. (2014). Dopamine D2-like receptors modulate unconditioned fear: Role of the inferior colliculus. PLoS One, 9(8), e104228. doi:10.1371/journal.pone.0104228Find this resource:

de Oliveira, R. P., Nagaishi, K. Y., & Barbosa Silva, R. C. (2017). Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats. Behavioural Brain Research, 325(Pt A), 72–78. doi:10.1016/j.bbr.2017.01.053Find this resource:

Ebert, U. (1996). Noradrenalin enhances the activity of cochlear nucleus neurons in the rat. European Journal of Neuroscience, 8(6), 1306–1314.Find this resource:

Ebert, U., & Ostwald, J. (1992). Serotonin modulates auditory information processing in the cochlear nucleus of the rat. Neuroscience Letters, 145(1), 51–54.Find this resource:

Eid, L., Champigny, M. F., Parent, A., & Parent, M. (2013). Quantitative and ultrastructural study of serotonin innervation of the globus pallidus in squirrel monkeys. European Journal of Neuroscience, 37(10), 1659–1668. doi:10.1111/ejn.12164Find this resource:

Elgoyhen, A. B., & Katz, E. (2012). The efferent medial olivocochlear-hair cell synapse. Journal of Physiology Paris, 106(1–2), 47–56. doi:10.1016/j.jphysparis.2011.06.001Find this resource:

Felix, R. A., 2nd, Elde, C. J., Nevue, A. A., & Portfors, C. V. (2017). Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse. Hearing Research, 344, 13–23. doi:10.1016/j.heares.2016.10.017Find this resource:

Fendt, M., Li, L., & Yeomans, J. S. (2001). Brain stem circuits mediating prepulse inhibition of the startle reflex. Psychopharmacology (Berlin), 156(2–3), 216–224.Find this resource:

Fischer, A. G., & Ullsperger, M. (2017). An Update on the Role of Serotonin and its Interplay with Dopamine for Reward. Frontiers in Human Neuroscience, 11, 484. doi:10.3389/fnhum.2017.00484Find this resource:

Fitzgerald, K. K., & Sanes, D. H. (1999). Serotonergic modulation of synapses in the developing gerbil lateral superior olive. Journal of Neurophysiology, 81(6), 2743–2752. doi:10.1152/jn.1999.81.6.2743Find this resource:

Foote, S. L., Aston-Jones, G., & Bloom, F. E. (1980). Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proceedings of the National Academy of Sciences of the United States of America, 77(5), 3033–3037.Find this resource:

Forlano, P. M., & Sisneros, J. A. (2016). Neuroanatomical evidence for catecholamines as modulators of audition and acoustic behavior in a vocal teleost. Advances in Experimental Medical Biology, 877, 439–475. doi:10.1007/978-3-319-21059-9_19Find this resource:

Fujino, K., & Oertel, D. (2001). Cholinergic modulation of stellate cells in the mammalian ventral cochlear nucleus. Journal of Neuroscience, 21(18), 7372–7383.Find this resource:

Fumero, B., Fernandez-Vera, J. R., Gonzalez-Mora, J. L., & Mas, M. (1994). Changes in monoamine turnover in forebrain areas associated with masculine sexual behavior: a microdialysis study. Brain Research, 662(1–2), 233–239.Find this resource:

Fuxe, K., Agnati, L. F., Marcoli, M., & Borroto-Escuela, D. O. (2015). Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets. Neurochemistry Research, 40(12), 2600–2614. doi:10.1007/s11064-015-1574-5Find this resource:

Fyk-Kolodziej, B. E., Shimano, T., Gafoor, D., Mirza, N., Griffith, R. D., Gong, T. W., & Holt, A. G. (2015). Dopamine in the auditory brainstem and midbrain: co-localization with amino acid neurotransmitters and gene expression following cochlear trauma. Frontiers in Neuroanatomy, 9, 88. doi:10.3389/fnana.2015.00088Find this resource:

Gittelman, J. X., Perkel, D. J., & Portfors, C. V. (2013). Dopamine modulates auditory responses in the inferior colliculus in a heterogeneous manner. Journal of the Association of Research Otolaryngology, 14(5), 719–729. doi:10.1007/s10162-013-0405-0Find this resource:

Gomez-Nieto, R., Rubio, M. E., & Lopez, D. E. (2008). Cholinergic input from the ventral nucleus of the trapezoid body to cochlear root neurons in rats. Journal of Comparative Neurology, 506(3), 452–468. doi:10.1002/cne.21554Find this resource:

Goyer, D., Kurth, S., Gillet, C., Keine, C., Rubsamen, R., & Kuenzel, T. (2016). Slow cholinergic modulation of spike probability in ultra-fast time-coding sensory neurons. eNeuro, 3(5). doi:10.1523/ENEURO.0186-16.2016Find this resource:

Habbicht, H., & Vater, M. (1996). A microiontophoretic study of acetylcholine effects in the inferior colliculus of horseshoe bats: implications for a modulatory role. Brain Research, 724(2), 169–179.Find this resource:

Hall, I. C., Rebec, G. V., & Hurley, L. M. (2010). Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli. Journal of Experimental Biology, 213(Pt 7), 1009–1017. doi:10.1242/jeb.035956Find this resource:

Hall, I. C., Sell, G. L., Chester, E. M., & Hurley, L. M. (2012). Stress-evoked increases in serotonin in the auditory midbrain do not directly result from elevations in serum corticosterone. Behavioural Brain Research, 226(1), 41–49. doi:10.1016/j.bbr.2011.08.042Find this resource:

Hall, I. C., Sell, G. L., & Hurley, L. M. (2011). Social regulation of serotonin in the auditory midbrain. Behavioral Neuroscience, 125(4), 501–511. doi:10.1037/a0024426Find this resource:

Hanson, J. L., & Hurley, L. M. (2014). Context-dependent fluctuation of serotonin in the auditory midbrain: the influence of sex, reproductive state and experience. Journal of Experimental Biology, 217(Pt 4), 526–535. doi:10.1242/jeb.087627Find this resource:

Hanson, J. L., & Hurley, L. M. (2016). Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus. Behavioral Neuroscience, 130(6), 600–613. doi:10.1037/bne0000165Find this resource:

Harris-Warrick, R. M., & Johnson, B. R. (2010). Checks and balances in neuromodulation. Frontiers in Behavioral Neuroscience, 4. doi:10.3389/fnbeh.2010.00047Find this resource:

He, S., Wang, Y. X., Petralia, R. S., & Brenowitz, S. D. (2014). Cholinergic modulation of large-conductance calcium-activated potassium channels regulates synaptic strength and spine calcium in cartwheel cells of the dorsal cochlear nucleus. Journal of Neuroscience, 34(15), 5261–5272. doi:10.1523/JNEUROSCI.3728-13.2014Find this resource:

Heym, J., Trulson, M. E., & Jacobs, B. L. (1982). Raphe unit activity in freely moving cats: effects of phasic auditory and visual stimuli. Brain Research, 232(1), 29–39.Find this resource:

Holt, A. G., Asako, M., Lomax, C. A., MacDonald, J. W., Tong, L., Lomax, M. I., & Altschuler, R. A. (2005). Deafness-related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity. Journal of Neurochemistry, 93(5), 1069–1086. doi:10.1111/j.1471-4159.2005.03090.xFind this resource:

Hormigo, S., Horta Junior Jde, A., Gomez-Nieto, R., & Lopez, D. E. (2012). The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats. Frontiers in Neural Circuits, 6, 41. doi:10.3389/fncir.2012.00041Find this resource:

Hurley, L. M. (2006). Different serotonin receptor agonists have distinct effects on sound-evoked responses in inferior colliculus. Journal of Neurophysiology, 96(5), 2177–2188. doi:10.1152/jn.00046.2006Find this resource:

Hurley, L. M. (2007). Activation of the serotonin 1A receptor alters the temporal characteristics of auditory responses in the inferior colliculus. Brain Research, 1181, 21–29. doi:10.1016/j.brainres.2007.08.053Find this resource:

Hurley, L. M., Devilbiss, D. M., & Waterhouse, B. D. (2004). A matter of focus: Monoaminergic modulation of stimulus coding in mammalian sensory networks. Current Opinion in Neurobiology, 14(4), 488–495. doi:10.1016/j.conb.2004.06.007Find this resource:

Hurley, L. M., & Hall, I. C. (2011). Context-dependent modulation of auditory processing by serotonin. Hearing Research, 279(1–2), 74–84. doi:10.1016/j.heares.2010.12.015Find this resource:

Hurley, L. M., & Pollak, G. D. (1999). Serotonin differentially modulates responses to tones and frequency-modulated sweeps in the inferior colliculus. Journal of Neuroscience, 19(18), 8071–8082.Find this resource:

Hurley, L. M., & Pollak, G. D. (2001). Serotonin effects on frequency tuning of inferior colliculus neurons. Journal of Neurophysiology, 85(2), 828–842. doi:10.1152/jn.2001.85.2.828Find this resource:

Hurley, L. M., & Pollak, G. D. (2005a). Serotonin modulates responses to species-specific vocalizations in the inferior colliculus. Journal of Comparative Physiology, A. Neuroethology, Sensory, Neural, and Behavioral Physiology, 191(6), 535–546. doi:10.1007/s00359-005-0623-yFind this resource:

Hurley, L. M., & Pollak, G. D. (2005b). Serotonin shifts first-spike latencies of inferior colliculus neurons. Journal of Neuroscience, 25(34), 7876–7886. doi:10.1523/JNEUROSCI.1178-05.2005Find this resource:

Hurley, L. M., & Sullivan, M. R. (2012). From behavioral context to receptors: serotonergic modulatory pathways in the IC. Frontiers in Neural Circuits, 6, 58. doi:10.3389/fncir.2012.00058Find this resource:

Hurley, L. M., & Thompson, A. M. (2001). Serotonergic innervation of the auditory brainstem of the Mexican free-tailed bat, Tadarida brasiliensis. Journal of Comparative Neurology, 435(1), 78–88.Find this resource:

Hurley, L. M., Tracy, J. A., & Bohorquez, A. (2008). Serotonin 1B receptor modulates frequency response curves and spectral integration in the inferior colliculus by reducing GABAergic inhibition. Journal of Neurophysiology, 100(3), 1656–1667. doi:10.1152/jn.90536.2008Find this resource:

Ito, T., Bishop, D. C., & Oliver, D. L. (2009). Two classes of GABAergic neurons in the inferior colliculus. Journal of Neuroscience, 29(44), 13860–13869. doi:10.1523/JNEUROSCI.3454-09.2009Find this resource:

Jacobs, B. L., Foote, S. L., & Bloom, F. E. (1978). Differential projections of neurons within the dorsal raphe nucleus of the rat: A horseradish peroxidase (HRP) study. Brain Research, 147(1), 149–153.Find this resource:

Janusonis, S. (2017). Serotonin in space: Understanding single fibers. ACS Chemical Neuroscience, 8(5), 893–896. doi:10.1021/acschemneuro.6b00417Find this resource:

Janusonis, S., Fite, K. V., & Foote, W. (1999). Topographic organization of serotonergic dorsal raphe neurons projecting to the superior colliculus in the Mongolian gerbil (Meriones unguiculatus). Journal of Comparative Neurology, 413(2), 342–355.Find this resource:

Kamke, M. R., Brown, M., & Irvine, D. R. (2005). Origin and immunolesioning of cholinergic basal forebrain innervation of cat primary auditory cortex. Hearing Research, 206(1–2), 89–106. doi:10.1016/j.heares.2004.12.014Find this resource:

Keesom, S. M., & Hurley, L. M. (2016). Socially induced serotonergic fluctuations in the male auditory midbrain correlate with female behavior during courtship. Journal of Neurophysiology, 115(4), 1786–1796. doi:10.1152/jn.00742.2015Find this resource:

Keesom, S. M., Morningstar, M. D., Sandlain, R., Wise, B. M., & Hurley, L. M. (2018). Social isolation reduces serotonergic fiber density in the inferior colliculus of female, but not male, mice. Brain Research, 1694, 94–103. doi:10.1016/j.brainres.2018.05.010Find this resource:

Keesom, S. M., Sloss, B. G., Erbowor-Becksen, Z., & Hurley, L. M. (2017). Social experience alters socially induced serotonergic fluctuations in the inferior colliculus. Journal of Neurophysiology, 118(6), 3230–3241. doi:10.1152/jn.00431.2017Find this resource:

Kirifides, M. L., Simpson, K. L., Lin, R. C., & Waterhouse, B. D. (2001). Topographic organization and neurochemical identity of dorsal raphe neurons that project to the trigeminal somatosensory pathway in the rat. Journal of Comparative Neurology, 435(3), 325–340.Find this resource:

Klepper, A., & Herbert, H. (1991). Distribution and origin of noradrenergic and serotonergic fibers in the cochlear nucleus and inferior colliculus of the rat. Brain Research, 557(1–2), 190–201.Find this resource:

Ko, K. W., Rasband, M. N., Meseguer, V., Kramer, R. H., & Golding, N. L. (2016). Serotonin modulates spike probability in the axon initial segment through HCN channels. Nature Neuroscience, 19(6), 826–834. doi:10.1038/nn.4293Find this resource:

Koch, M., Kungel, M., & Herbert, H. (1993). Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat. Experimental Brain Research, 97(1), 71–82.Find this resource:

Korzan, W. J., & Summers, C. H. (2007). Behavioral diversity and neurochemical plasticity: Selection of stress coping strategies that define social status. Brain Behavior and Evolution, 70(4), 257–266. doi:10.1159/000105489Find this resource:

Kössl, M., & Vater, M. (1989). Noradrenaline enhances temporal auditory contrast and neuronal timing precision in the cochlear nucleus of the mustached bat. Journal of Neuroscience, 9(12), 4169–4178.Find this resource:

Kössl, M., Vater, M., & Schweizer, H. (1988). Distribution of catecholamine fibers in the cochlear nucleus of horseshoe bats and mustache bats. Journal of Comparative Neurology, 269(4), 523–534. doi:10.1002/cne.902690405Find this resource:

Kromer, L. F., & Moore, R. Y. (1976). Cochlear nucleus innervation by central norepinephrine neurons in the rat. Brain Research, 118(3), 531–537.Find this resource:

Kuo, S. P., & Trussell, L. O. (2011). Spontaneous spiking and synaptic depression underlie noradrenergic control of feed-forward inhibition. Neuron, 71(2), 306–318. doi:10.1016/j.neuron.2011.05.039Find this resource:

Leao, R. M., & Von Gersdorff, H. (2002). Noradrenaline increases high-frequency firing at the calyx of Held synapse during development by inhibiting glutamate release. Journal of Neurophysiology, 87(5), 2297–2306. doi:10.1152/jn.2002.87.5.2297Find this resource:

LeDoux, J. E., Ruggiero, D. A., & Reis, D. J. (1985). Projections to the subcortical forebrain from anatomically defined regions of the medial geniculate body in the rat. Journal of Comparative Neurology, 242(2), 182–213. doi:10.1002/cne.902420204Find this resource:

Lee, H. S., Kim, M. A., Valentino, R. J., & Waterhouse, B. D. (2003). Glutamatergic afferent projections to the dorsal raphe nucleus of the rat. Brain Research, 963(1–2), 57–71.Find this resource:

Lee, S. B., Beak, S. K., Park, S. H., Waterhouse, B. D., & Lee, H. S. (2009). Collateral projection from the locus coeruleus to whisker-related sensory and motor brain regions of the rat. Journal of Comparative Neurology, 514(4), 387–402. doi:10.1002/cne.22012Find this resource:

Leitner, D. S., & Cohen, M. E. (1985). Role of the inferior colliculus in the inhibition of acoustic startle in the rat. Physiology and Behavior, 34(1), 65–70.Find this resource:

Lesicko, A. M., Hristova, T. S., Maigler, K. C., & Llano, D. A. (2016). Connectional modularity of top-down and bottom-up multimodal inputs to the lateral cortex of the mouse inferior colliculus. Journal of Neuroscience, 36(43), 11037–11050. doi:10.1523/JNEUROSCI.4134-15.2016Find this resource:

Levitt, P., & Moore, R. Y. (1979). Origin and organization of brainstem catecholamine innervation in the rat. Journal of Comparative Neurology, 186(4), 505–528. doi:10.1002/cne.901860402Find this resource:

Li, L., Korngut, L. M., Frost, B. J., & Beninger, R. J. (1998a). Prepulse inhibition following lesions of the inferior colliculus: prepulse intensity functions. Physiology and Behavior, 65(1), 133–139.Find this resource:

Li, L., Priebe, R. P., & Yeomans, J. S. (1998b). Prepulse inhibition of acoustic or trigeminal startle of rats by unilateral electrical stimulation of the inferior colliculus. Behavioral Neuroscience, 112(5), 1187–1198.Find this resource:

Li, L., & Yue, Q. (2002). Auditory gating processes and binaural inhibition in the inferior colliculus. Hearing Research, 168(1–2), 98–109.Find this resource:

Linster, C., & Cleland, T. A. (2016). Neuromodulation of olfactory transformations. Current Opinion in Neurobiology, 40, 170–177. doi:10.1016/j.conb.2016.07.006Find this resource:

Loftus, W. C., Bishop, D. C., & Oliver, D. L. (2010). Differential patterns of inputs create functional zones in central nucleus of inferior colliculus. Journal of Neuroscience, 30(40), 13396–13408. doi:10.1523/JNEUROSCI.0338-10.2010Find this resource:

Lorincz, M. L., & Adamantidis, A. R. (2017). Monoaminergic control of brain states and sensory processing: Existing knowledge and recent insights obtained with optogenetics. Progress in Neurobiology, 151, 237–253. doi:10.1016/j.pneurobio.2016.09.003Find this resource:

Luppi, P. H., Aston-Jones, G., Akaoka, H., Chouvet, G., & Jouvet, M. (1995). Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin. Neuroscience, 65(1), 119–160.Find this resource:

Ma, X., & Suga, N. (2005). Long-term cortical plasticity evoked by electric stimulation and acetylcholine applied to the auditory cortex. Proceedings of the National Academy of Sciences of the United States of America, 102(26), 9335–9340. doi:10.1073/pnas.0503851102Find this resource:

Macedo, C. E., Castilho, V. M., de Souza e Silva, M. A., & Brandao, M. L. (2002). Dual 5-HT mechanisms in basolateral and central nuclei of amygdala in the regulation of the defensive behavior induced by electrical stimulation of the inferior colliculus. Brain Research Bulletin, 59(3), 189–195.Find this resource:

Macedo, C. E., Martinez, R. C., Albrechet-Souza, L., Molina, V. A., & Brandao, M. L. (2007). 5-HT2- and D1-mechanisms of the basolateral nucleus of the amygdala enhance conditioned fear and impair unconditioned fear. Behavioural Brain Research, 177(1), 100–108. doi:10.1016/j.bbr.2006.10.031Find this resource:

Macedo, C. E., Martinez, R. C., de Souza Silva, M. A., & Brandao, M. L. (2005). Increases in extracellular levels of 5-HT and dopamine in the basolateral, but not in the central, nucleus of amygdala induced by aversive stimulation of the inferior colliculus. European Journal of Neuroscience, 21(4), 1131–1138. doi:10.1111/j.1460-9568.2005.03939.xFind this resource:

Maisonnette, S. S., Kawasaki, M. C., Coimbra, N. C., & Brandao, M. L. (1996). Effects of lesions of amygdaloid nuclei and substantia nigra on aversive responses induced by electrical stimulation of the inferior colliculus. Brain Research Bulletin, 40(2), 93–98.Find this resource:

Maley, B. E., Engle, M. G., Humphreys, S., Vascik, D. A., Howes, K. A., Newton, B. W., & Elde, R. P. (1990). Monoamine synaptic structure and localization in the central nervous system. Journal of Electron Microscopic Technique, 15(1), 20–33. doi:10.1002/jemt.1060150104Find this resource:

Maney, D. L. (2013). The incentive salience of courtship vocalizations: Hormone-mediated “wanting” in the auditory system. Hearing Research, 305, 19–30. doi:10.1016/j.heares.2013.04.011Find this resource:

Marder, E. (2012). Neuromodulation of neuronal circuits: back to the future. Neuron, 76(1), 1–11. doi:10.1016/j.neuron.2012.09.010Find this resource:

Marder, E., & Bucher, D. (2007). Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs. Annual Review of Physiology, 69, 291–316. doi:10.1146/annurev.physiol.69.031905.161516Find this resource:

Marlin, B. J., Mitre, M., D'Amour J. A., Chao, M. V., & Froemke, R. C. (2015). Oxytocin enables maternal behaviour by balancing cortical inhibition. Nature, 520(7548), 499–504. doi:10.1038/nature14402Find this resource:

Marsh, R. A., Fuzessery, Z. M., Grose, C. D., & Wenstrup, J. J. (2002). Projection to the inferior colliculus from the basal nucleus of the amygdala. Journal of Neuroscience, 22(23), 10449–10460.Find this resource:

Martins, A. R., & Froemke, R. C. (2015). Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex. Nature Neuroscience, 18(10), 1483–1492. doi:10.1038/nn.4090Find this resource:

Mas, M., Fumero, B., & Gonzalez-Mora, J. L. (1995). Voltammetric and microdialysis monitoring of brain monoamine neurotransmitter release during sociosexual interactions. Behavioural Brain Research, 71(1–2), 69–79.Find this resource:

Matragrano, L. L., Beaulieu, M., Phillip, J. O., Rae, A. I., Sanford, S. E., Sockman, K. W., & Maney, D. L. (2012a). Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway. PLoS One, 7(6), e39388. doi:10.1371/journal.pone.0039388Find this resource:

Matragrano, L. L., LeBlanc, M. M., Chitrapu, A., Blanton, Z. E., & Maney, D. L. (2013). Testosterone alters genomic responses to song and monoaminergic innervation of auditory areas in a seasonally breeding songbird. Developmental Neurobiology, 73(6), 455–468. doi:10.1002/dneu.22072Find this resource:

Matragrano, L. L., Sanford, S. E., Salvante, K. G., Beaulieu, M., Sockman, K. W., & Maney, D. L. (2012b). Estradiol-dependent modulation of serotonergic markers in auditory areas of a seasonally breeding songbird. Behavioral Neuroscience, 126(1), 110–122. doi:10.1037/a0025586Find this resource:

McCormick, D. A., & Pape, H. C. (1990). Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones. Journal of Physiology, 431, 319–342.Find this resource:

Mellott, J. G., Motts, S. D., & Schofield, B. R. (2011). Multiple origins of cholinergic innervation of the cochlear nucleus. Neuroscience, 180, 138–147. doi:10.1016/j.neuroscience.2011.02.010Find this resource:

Melo, L. L., & Brandao, M. L. (1995). Role of 5-HT1A and 5-HT2 receptors in the aversion induced by electrical stimulation of inferior colliculus. Pharmacology, Biochemistry, and Behavior, 51(2–3), 317–321.Find this resource:

Mena-Segovia, J., & Bolam, J. P. (2017). Rethinking the pedunculopontine nucleus: From cellular organization to function. Neuron, 94(1), 7–18. doi:10.1016/j.neuron.2017.02.027Find this resource:

Miko, I. J., & Sanes, D. H. (2009). Transient gain adjustment in the inferior colliculus is serotonin- and calcium-dependent. Hearing Research, 251(1–2), 39–50. doi:10.1016/j.heares.2009.02.003Find this resource:

Mizutani, H., Hori, T., & Takahashi, T. (2006). 5-HT1B receptor-mediated presynaptic inhibition at the calyx of Held of immature rats. European Journal of Neuroscience, 24(7), 1946–1954. doi:10.1111/j.1460-9568.2006.05063.xFind this resource:

Motts, S. D., & Schofield, B. R. (2009). Sources of cholinergic input to the inferior colliculus. Neuroscience, 160(1), 103–114. doi:10.1016/j.neuroscience.2009.02.036Find this resource:

Mulders, W. H., & Robertson, D. (2000). Morphological relationships of peptidergic and noradrenergic nerve terminals to olivocochlear neurones in the rat. Hearing Research, 144(1–2), 53–64.Find this resource:

Mulders, W. H., & Robertson, D. (2001). Origin of the noradrenergic innervation of the superior olivary complex in the rat. Journal of Chemical Neuroanatomy, 21(4), 313–322.Find this resource:

Mulders, W. H., & Robertson, D. (2004). Dopaminergic olivocochlear neurons originate in the high frequency region of the lateral superior olive of guinea pigs. Hearing Research, 187(1–2), 122–130.Find this resource:

Mulders, W. H., & Robertson, D. (2005a). Catecholaminergic innervation of guinea pig superior olivary complex. Journal of Chemical Neuroanatomy, 30(4), 230–242. doi:10.1016/j.jchemneu.2005.09.005Find this resource:

Mulders, W. H., & Robertson, D. (2005b). Noradrenergic modulation of brainstem nuclei alters cochlear neural output. Hearing Research, 204, 147–155.Find this resource:

Nadim, F., & Bucher, D. (2014). Neuromodulation of neurons and synapses. Current Opinion in Neurobiology, 29, 48–56. doi:10.1016/j.conb.2014.05.003Find this resource:

Nevue, A. A., Elde, C. J., Perkel, D. J., & Portfors, C. V. (2016a). Dopaminergic input to the inferior colliculus in mice. Frontiers in Neuroanatomy, 9, 168. doi:10.3389/fnana.2015.00168Find this resource:

Nevue, A. A., Felix, R. A., 2nd, & Portfors, C. V. (2016b). Dopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem. Hearing Research, 341, 202–209. doi:10.1016/j.heares.2016.09.001Find this resource:

Niederkofler, V., Asher, T. E., Okaty, B. W., Rood, B. D., Narayan, A., Hwa, L. S., … Dymecki, S. M. (2016). Identification of serotonergic neuronal modules that affect aggressive behavior. Cell Reports, 17(8), 1934–1949. doi:10.1016/j.celrep.2016.10.063Find this resource:

Nobre, M. J., & Brandao, M. L. (2011). Modulation of auditory-evoked potentials recorded in the inferior colliculus by GABAergic mechanisms in the basolateral and central nuclei of the amygdala in high- and low-anxiety rats. Brain Research, 1421, 20–29. doi:10.1016/j.brainres.2011.09.013Find this resource:

Nobre, M. J., Lopes, M. G., & Brandao, M. L. (2004). Defense reaction mediated by NMDA mechanisms in the inferior colliculus is modulated by GABAergic nigro-collicular pathways. Brain Research, 999(1), 124–131.Find this resource:

Obara, N., Kamiya, H., & Fukuda, S. (2014). Serotonergic modulation of inhibitory synaptic transmission in mouse inferior colliculus. Biomedical Research, 35(1), 81–84.Find this resource:

Ohno, Y. (2010). New insight into the therapeutic role of 5-HT1A receptors in central nervous system disorders. Central Nervous System Agents in Medical Chemistry, 10(2), 148–157.Find this resource:

Olazábal, U. E., & Moore, J. K. (1989). Nigrotectal projection to the inferior colliculus: Horseradish peroxidase transport and tyrosine hydroxylase immunohistochemical studies in rats, cats, and bats. Journal of Comparative Neurology, 282(1), 98–118. doi:10.1002/cne.902820108Find this resource:

Papesh, M. A., & Hurley, L. M. (2012). Plasticity of serotonergic innervation of the inferior colliculus in mice following acoustic trauma. Hearing Research, 283(1–2), 89–97. doi:10.1016/j.heares.2011.11.004Find this resource:

Papesh, M. A., & Hurley, L. M. (2016). Modulation of auditory brainstem responses by serotonin and specific serotonin receptors. Hearing Research, 332, 121–136. doi:10.1016/j.heares.2015.11.014Find this resource:

Parent, A., Descarries, L., & Beaudet, A. (1981). Organization of ascending serotonin systems in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine. Neuroscience, 6(2), 115–138.Find this resource:

Patel, M. B., Sons, S., Yudintsev, G., Lesicko, A. M., Yang, L., Taha, G. A., … Llano, D. A. (2017). Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse. Journal of Comparative Neurology, 525(4), 885–900. doi:10.1002/cne.24106Find this resource:

Peruzzi, D., Bartlett, E., Smith, P. H., & Oliver, D. L. (1997). A monosynaptic GABAergic input from the inferior colliculus to the medial geniculate body in rat. Journal of Neuroscience, 17(10), 3766–3777.Find this resource:

Peruzzi, D., & Dut, A. (2004). GABA, serotonin and serotonin receptors in the rat inferior colliculus. Brain Research, 998(2), 247–250.Find this resource:

Petersen, C. L., & Hurley, L. M. (2017). Putting it in context: linking auditory processing with social behavior circuits in the vertebrate brain. Integrative and Comparative Biology, 57(4), 865–877.Find this resource:

Peyron, C., Petit, J. M., Rampon, C., Jouvet, M., & Luppi, P. H. (1998). Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience, 82(2), 443–468.Find this resource:

Pollak Dorocic, I., Furth, D., Xuan, Y., Johansson, Y., Pozzi, L., Silberberg, G., … Meletis, K. (2014). A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron, 83(3), 663–678. doi:10.1016/j.neuron.2014.07.002Find this resource:

Pollak, G. D. (2013). The dominant role of inhibition in creating response selectivities for communication calls in the brainstem auditory system. Hearing Research, 305, 86–101. doi:10.1016/j.heares.2013.03.001Find this resource:

Pollak, G. D., Burger, R. M., Park, T. J., Klug, A., & Bauer, E. E. (2002). Roles of inhibition for transforming binaural properties in the brainstem auditory system. Hearing Research, 168(1–2), 60–78.Find this resource:

Pollak, G. D., Xie, R., Gittelman, J. X., Andoni, S., & Li, N. (2011). The dominance of inhibition in the inferior colliculus. Hearing Research, 274(1–2), 27–39. doi:10.1016/j.heares.2010.05.010Find this resource:

Rasmussen, K., Strecker, R. E., & Jacobs, B. L. (1986). Single unit responses of noradrenergic, serotonergic, and dopaminergic neurons in freely moving cats to simple sensory stimuli. Brain Research, 369(1–2), 336–340.Find this resource:

Reese, N. B., Garcia-Rill, E., & Skinner, R. D. (1995a). Auditory input to the pedunculopontine nucleus: II. Unit responses. Brain Research Bulletin, 37(3), 265–273.Find this resource:

Reese, N. B., Garcia-Rill, E., & Skinner, R. D. (1995b). The pedunculopontine nucleus—auditory input, arousal and pathophysiology. Progress in Neurobiology, 47(2), 105–133.Find this resource:

Retson, T. A., & Van Bockstaele, E. J. (2013). Coordinate regulation of noradrenergic and serotonergic brain regions by amygdalar neurons. Journal of Chemical Neuroanatomy, 52, 9–19. doi:10.1016/j.jchemneu.2013.04.003Find this resource:

Sakai, K., & Crochet, S. (2001). Differentiation of presumed serotonergic dorsal raphe neurons in relation to behavior and wake-sleep states. Neuroscience, 104(4), 1141–1155.Find this resource:

Sari, Y. (2004). Serotonin1B receptors: from protein to physiological function and behavior. Neuroscience and Biobehavior Reviews, 28(6), 565–582. doi:10.1016/j.neubiorev.2004.08.008Find this resource:

Satake, S., Yamada, K., Melo, L. L., & Barbosa Silva, R. (2012). Effects of microinjections of apomorphine and haloperidol into the inferior colliculus on prepulse inhibition of the acoustic startle reflex in rat. Neuroscience Letters, 509(1), 60–63. doi:10.1016/j.neulet.2011.12.052Find this resource:

Schofield, B. R. (2010). Projections from auditory cortex to midbrain cholinergic neurons that project to the inferior colliculus. Neuroscience, 166(1), 231–240. doi:10.1016/j.neuroscience.2009.12.008Find this resource:

Schofield, B. R., & Cant, N. B. (1999). Descending auditory pathways: projections from the inferior colliculus contact superior olivary cells that project bilaterally to the cochlear nuclei. Journal of Comparative Neurology, 409(2), 210–223.Find this resource:

Schofield, B. R., & Hurley, L. M. (2018). Circuits for modulation of auditory function. In D. O. Oliver, N. B. Cant, A. N. Popper, & R. R. Fay (Eds.), The mammalian auditory pathways: Synaptic organization and microcircuits (Vol. 65). New York, NY: Springer-Verlag.Find this resource:

Schofield, B. R., & Motts, S. D. (2009). Projections from auditory cortex to cholinergic cells in the midbrain tegmentum of guinea pigs. Brain Research Bulletin, 80(3), 163–170. doi:10.1016/j.brainresbull.2009.06.015Find this resource:

Schofield, B. R., Motts, S. D., & Mellott, J. G. (2011). Cholinergic cells of the pontomesencephalic tegmentum: Connections with auditory structures from cochlear nucleus to cortex. Hearing Research, 279(1–2), 85–95. doi:10.1016/j.heares.2010.12.019Find this resource:

Sherriff, F. E., & Henderson, Z. (1994). Cholinergic neurons in the ventral trapezoid nucleus project to the cochlear nuclei in the rat. Neuroscience, 58(3), 627–633.Find this resource:

Shima, K., Nakahama, H., & Yamamoto, M. (1986). Firing properties of two types of nucleus raphe dorsalis neurons during the sleep-waking cycle and their responses to sensory stimuli. Brain Research, 399(2), 317–326.Find this resource:

Smith, A. R., Kwon, J. H., Navarro, M., & Hurley, L. M. (2014). Acoustic trauma triggers upregulation of serotonin receptor genes. Hearing Research, 315, 40–48. doi:10.1016/j.heares.2014.06.004Find this resource:

Stark, H., & Scheich, H. (1997). Dopaminergic and serotonergic neurotransmission systems are differentially involved in auditory cortex learning: a long-term microdialysis study of metabolites. Journal of Neurochemistry, 68(2), 691–697.Find this resource:

Stornetta, R. L., Macon, C. J., Nguyen, T. M., Coates, M. B., & Guyenet, P. G. (2013). Cholinergic neurons in the mouse rostral ventrolateral medulla target sensory afferent areas. Brain Structure and Function, 218(2), 455–475. doi:10.1007/s00429-012-0408-3Find this resource:

Tadros, S. F., D'Souza, M., Zettel, M. L., Zhu, X., Lynch-Erhardt, M., & Frisina, R. D. (2007). Serotonin 2B receptor: upregulated with age and hearing loss in mouse auditory system. Neurobiology of Aging, 28(7), 1112–1123. doi:10.1016/j.neurobiolaging.2006.05.021Find this resource:

Tang, Z. Q., & Trussell, L. O. (2015). Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. Journal of Neuroscience, 35(11), 4540–4551. doi:10.1523/JNEUROSCI.4825-14.2015Find this resource:

Tang, Z. Q., & Trussell, L. O. (2017). Serotonergic modulation of sensory representation in a central multisensory circuit is pathway specific. Cell Reports, 20(8), 1844–1854. doi:10.1016/j.celrep.2017.07.079Find this resource:

Thompson, A. M., & Hurley, L. M. (2004). Dense serotonergic innervation of principal nuclei of the superior olivary complex in mouse. Neuroscience Letters, 356(3), 179–182. doi:10.1016/j.neulet.2003.11.052Find this resource:

Thompson, A. M., & Schofield, B. R. (2000). Afferent projections of the superior olivary complex. Microscopy Research Techniques, 51(4), 330–354. doi:10.1002/1097-0029(20001115)51:4<330::AID-JEMT4>3.0.CO;2-XFind this resource:

Thompson, A. M., & Thompson, G. C. (2001). Serotonin projection patterns to the cochlear nucleus. Brain Research, 907(1–2), 195–207.Find this resource:

Thompson, G. C., Thompson, A. M., Garrett, K. M., & Britton, B. H. (1994). Serotonin and serotonin receptors in the central auditory system. Otolaryngology—Head and Neck Surgery, 110(1), 93–102. doi:10.1177/019459989411000111Find this resource:

Tong, L., Altschuler, R. A., & Holt, A. G. (2005). Tyrosine hydroxylase in rat auditory midbrain: distribution and changes following deafness. Hearing Research, 206(1–2), 28–41. doi:10.1016/j.heares.2005.03.006Find this resource:

Van Bockstaele, E. J., Biswas, A., & Pickel, V. M. (1993). Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens. Brain Research, 624(1–2), 188–198.Find this resource:

Vasudeva, R. K., Lin, R. C., Simpson, K. L., & Waterhouse, B. D. (2011). Functional organization of the dorsal raphe efferent system with special consideration of nitrergic cell groups. Journal of Chemical Neuroanatomy, 41(4), 281–293. doi:10.1016/j.jchemneu.2011.05.008Find this resource:

Villar, M. J., Vitale, M. L., Hokfelt, T., & Verhofstad, A. A. (1988). Dorsal raphe serotoninergic branching neurons projecting both to the lateral geniculate body and superior colliculus: a combined retrograde tracing-immunohistochemical study in the rat. Journal of Comparative Neurology, 277(1), 126–140. doi:10.1002/cne.902770109Find this resource:

Wang, H. T., Luo, B., Huang, Y. N., Zhou, K. Q., & Chen, L. (2008). Sodium salicylate suppresses serotonin-induced enhancement of GABAergic spontaneous inhibitory postsynaptic currents in rat inferior colliculus in vitro. Hearing Research, 236(1–2), 42–51. doi:10.1016/j.heares.2007.11.015Find this resource:

Wang, J., Palkovits, M., Usdin, T. B., & Dobolyi, A. (2006). Afferent connections of the subparafascicular area in rat. Neuroscience, 138(1), 197–220. doi:10.1016/j.neuroscience.2005.11.010Find this resource:

Wang, X., & Robertson, D. (1997). Effects of bioamines and peptides on neurones in the ventral nucleus of trapezoid body and rostral periolivary regions of the rat superior olivary complex: An in vitro investigation. Hearing Research, 106(1–2), 20–28.Find this resource:

Waterhouse, B. D., Border, B., Wahl, L., & Mihailoff, G. A. (1993). Topographic organization of rat locus coeruleus and dorsal raphe nuclei: distribution of cells projecting to visual system structures. Journal of Comparative Neurology, 336(3), 345–361. doi:10.1002/cne.903360304Find this resource:

Waterhouse, B. D., Mihailoff, G. A., Baack, J. C., & Woodward, D. J. (1986). Topographical distribution of dorsal and median raphe neurons projecting to motor, sensorimotor, and visual cortical areas in the rat. Journal of Comparative Neurology, 249(4), 460–476, 478–481.Find this resource:

Weinberger, N. M. (2015). New perspectives on the auditory cortex: Learning and memory. Handbook of Clinical Neurology, 129, 117–147. doi:10.1016/B978-0-444-62630-1.00007-XFind this resource:

Woods, C. I., & Azeredo, W. J. (1999). Noradrenergic and serotonergic projections to the superior olive: Potential for modulation of olivocochlear neurons. Brain Research, 836(1–2), 9–18.Find this resource:

Wynne, B., & Robertson, D. (1996). Localization of dopamine-beta-hydroxylase-like immunoreactivity in the superior olivary complex of the rat. Audiology and Neurotology, 1(1), 54–64.Find this resource:

Yamada, R., Kuba, H., Ishii, T. M., & Ohmori, H. (2005). Hyperpolarization-activated cyclic nucleotide-gated cation channels regulate auditory coincidence detection in nucleus laminaris of the chick. Journal of Neuroscience, 25, 8867–8877.Find this resource:

Yasui, Y., Kayahara, T., Nakano, K., & Mizuno, N. (1990). The subparafascicular thalamic nucleus of the rat receives projection fibers from the inferior colliculus and auditory cortex. Brain Research, 537(1–2), 323–327.Find this resource:

Yasui, Y., Nakano, K., & Mizuno, N. (1992). Descending projections from the subparafascicular thalamic nucleus to the lower brain stem in the rat. Experimental Brain Research, 90(3), 508-518.Find this resource:

Yeomans, J. S., Lee, J., Yeomans, M. H., Steidl, S., & Li, L. (2006). Midbrain pathways for prepulse inhibition and startle activation in rat. Neuroscience, 142(4), 921–929. doi:10.1016/j.neuroscience.2006.06.025Find this resource:

Yigit, M., Keipert, C., & Backus, K. H. (2003). Muscarinic acetylcholine receptors potentiate the GABAergic transmission in the developing rat inferior colliculus. Neuropharmacology, 45(4), 504–513.Find this resource:

Zhou, J., & Shore, S. (2006). Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the guinea pig. Journal of Comparative Neurology, 495(1), 100–112. doi:10.1002/cne.20863Find this resource: