title: The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.
abstract: The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss.
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Daniël O J
authors.initials: DOJ
authors.lastname: Reijntjes
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: s.pyott@umcg.nl.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Pyott
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology; D005849:Gerbillinae; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D034381:Hearing Loss; D006801:Humans; D051379:Mice; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D055366:Synaptic Potentials; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D004298:Dopamine
keywords: Auditory neuropathy and synaptopathy; Cochlea; Inner hair cells; Ion channels and transporters; Lateral olivocochlear efferents; Neurotransmitter receptors; Postsynaptic density; Type I spiral ganglion neurons