Reception of chemicals via olfaction and gustation are prerequisites to find, distinguish, and recognize food and mates and to avoid dangers. Several receptor gene superfamilies are employed in arthropod chemosensation: inverse 7-transmembrane (7-TM) gustatory and olfactory receptors (GRs, ORs), 3-TM ionotropic glutamate-related receptors (IRs), receptor-guanylyl cyclases, transient receptor potential ion channels, and epithelial sodium channels. Some of these receptor gene families have ancient origins and expanded in several taxa, producing very large, variant gene families adapted to the respectively relevant odor ligands in species-specific environments. Biochemical and electrophysiological studies in situ as well as molecular genetics found evidence for G-protein-dependent signal transduction cascades for ORs, GRs, and IRs, suggesting that signal amplification is paramount for chemical senses. In contrast, heterologous expression studies argued for primarily ionotropic transduction as a prerequisite to interstimulus intervals in the range of microseconds.
Martin Wallner, Anne Kerstin Lindemeyer, and Richard W. Olsen
GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and mediate rapid synaptic as well as slow extrasynaptic inhibitory neurotransmission. Structurally, GABAARs are ligand-gated ion channels formed by a total of 19 homologous subunits, each with four transmembrane domains assembled as pentamers, forming a GABA-gated Cl– channels. The major classical synaptic GABAAR subtypes are formed by 2α2β and a γ subunit, with six different possible α subunits, three different β subunits, and three γ subunits, with the most abundant subtype, α1β2γ2 receptors. More recently, highly GABA-sensitive extrasynaptic δ subunit-containing receptors that are persistently (tonically) activated by low ambient levels of GABA have entered the limelight. GABAARs are targets for sedative/hypnotic and anxiolytic drugs (e.g., benzodiazepines [BZs] and other BZ site ligands), as well as general anesthetics (e.g., etomidate, propofol, barbiturate, and neurosteroid anesthetics, and possibly volatile agents and long-chain alcohols), and also are important targets for alcohol actions.
The main function of brains is to generate adaptive behavior. Far from being the stereotypical, robot-like insect, the fruit fly Drosophila exhibits astounding flexibility and chooses different courses of actions even under identical external circumstances. Due to the power of genetics, we now are beginning to understand the neuronal mechanisms underlying this behavioral flexibility. Interestingly, the evidence from studies of disparate behaviors converges on common organizational principles common to many if not all behaviors, such as modified sensory processing, involvement of biogenic amines in network remodeling, ongoing activity, and modulation by feedback. Seemingly foreseeing these recent insights, the first research fields in Drosophila behavioral neurogenetics reflected this constant negotiation between internal and external demands on the animal as the common mechanism underlying adaptive behavioral choice in Drosophila.
Jiaxing Li and Catherine A. Collins
In the face of acute or chronic axonal damage, neurons and their axons undergo a number of molecular, cellular, and morphological changes. These changes facilitate two types of responses, axonal degeneration and regeneration, both of which are remarkably conserved in both vertebrates and invertebrates. Invertebrate model organisms, including Drosophila and C. elegans, have offered a powerful platform with accessible genetic tools for manipulation and amenable nervous system for visualization. Thus far, several critical components and pathways in axonal degeneration and regeneration have been identified in invertebrate studies, including Sarm and Wallenda/DLK. This article highlights important findings in Drosophila, C. elegans, and other invertebrate injury models that have shed light upon the mechanism in axonal injury response.
Lynne A. Fieber
This chapter introduces working definitions of neuropeptides and neurotransmitters from the perspective of invertebrate physiological processes. Neuropeptides and neurotransmitters are intercellular chemical signaling agents used by all animals. Chemical signaling augments or substitutes for electrical communication in the nervous system. When these agents act as neurotransmitters, they convert electrical signals to chemical signals across the synapse. As hormones, they circulate from a site of release to act at a more distant site in the body of the organism. Neuropeptides and neurotransmitters are classified into these groups mostly on the basis of their molecular size. This article describes several neuropeptide superfamilies and their wide scope of actions in model invertebrates. The article also describes the main neurotransmitters used by invertebrates.
Roger L. Papke
Acetylcholine, exquisitely evolved as a neurotransmitter, is made and released by the neurons that take the integrated output of the central nervous system throughout the body. At both neuromuscular junctions and autonomic ganglia, acetylcholine activates synaptic ion channels that take their name from the plant alkaloid nicotine, which is a mimic of the natural neurotransmitter. This chapter begins with the scientific discoveries related to the nicotinic acetylcholine receptors (nAChR) of the neuromuscular junction and how resulting insights led to an understanding of the fundamentals of synaptic transmission. The nAChR are one member of a superfamily of ligand-gated ion channels, and although in the brain excitatory neurotransmission is mediated by another family of synaptic receptors that are gated by glutamate, nicotinic receptors are important modulators of brain function and significant targets for drug development. In the brain, nAChR are targets for cognitive disorders and, tragically, responsible for tobacco addiction.
Annette Nicke, Thomas Grutter, and Terrance M. Egan
P2X receptors are ATP-gated ion channels that are ubiquitously expressed in eukaryotic tissues. They are involved in diverse physiological processes, from modulation of synaptic transmission, to inflammation, sensing of taste, bladder filling, and pain. Research on these receptors was for a long time hampered by a complex pharmacology and lack of high-resolution structures. However, the use of novel and modern methods brought significant progress and insight into receptor function. This article reviews P2X receptor structure, molecular function, and cellular physiology, emphasizing recent studies using crystallography, optical tools, and gene ablation to describe the sequence of events leading from agonist binding to physiological response. These studies reveal remarkable structural and functional properties not found in other ligand-gated ion channels, but still relevant to the field as a whole.
Truus E. M. Abbink, Lisanne E. Wisse, Xuemin Wang, and Christopher G. Proud
Vanishing white matter (VWM) disease is a recessive disorder characterized by gradual loss of white matter and of myelin. Its clinical severity is high variable. VWM is caused by mutations in any one of the five genes encoding subunits of eukaryotic initiation factor 2B (eIF2B), a ubiquitous, multimeric protein that plays crucial roles in protein synthesis and its control. There are now known to be at least 160 mutations in eIF2B genes that lead to VWM. Where tested, most mutations impair the activity or integrity of the eIF2B complex. However, it remains unclear how and why defects in eIF2B lead to VWM. This article discusses recent advances in understanding the structure and functions of eIF2B and the pathogenic basis of VWM.
Yucheng Xiao, Zifan Pei, and Theodore R. Cummins
Voltage-gated sodium channels (VGSCs) in peripheral sensory neurons play a critical role in transmitting information regarding noxious stimuli from the periphery to the central nervous system. Multiple VGSCs are expressed in nociceptive neurons. Nociceptive neurons express fast, slow, and persistent VGSCs that can exhibit diverse pharmacology. It is proposed that these isoforms exhibit unique properties that are specifically tuned for the failsafe transmission of nociceptive information in spite of tissue damage. Genetic mutations in several isoforms can cause both loss of pain sensation and severe neuropathic pain sensations. Aberrant pain sensations associated with inherited and acquired pain conditions can be difficult to treat, but it is hoped that a detailed understanding of the structure and function of sensory neuronal VGSCs will aid the development of targeted isoform-specific inhibitors. This chapter reviews what is known about VGSCs that play specialized roles in pain transmission.