GABAergic synapses between auditory efferent neurons and type II spiral ganglion afferent neurons in the mouse cochlea

• 成果类型: Article
• 署名作者: Bachman, Julia L.; Kitcher, Sian R.; Vattino, Lucas G.; Beaulac, Holly J.; Chaves, M. Grace; Rivera, Israel Hernandez; Katz, Eleonora; Wedemeyer, Carolina; Weisz, Catherine J. C.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Harvard University; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13163
• DOI: 10.1073/pnas.2409921122
• 发表日期: 2025-02-25
• 关键词: outer hair-cells; crossed olivocochlear bundle; guinea-pig cochlea; electrical-stimulation; selective attention; transmitter release; parallel fiber; nerve response; hensens cells; innervation

摘要

Cochlear outer hair cells (OHCs) are electromotile and implicated in amplification of responses to sound that enhance sound sensitivity and frequency tuning. They send afferent information through glutamatergic synapses onto type II spiral ganglion neurons (SGNs). These synapses are weaker than those from cochlear inner hair cells onto type I SGN, suggesting that type II SGNs respond only to intense sound levels. OHCs also receive efferent innervation from medial olivocochlear (MOC) neurons. MOC neurons are cholinergic yet inhibit OHCs due to the functional coupling of alpha9/alpha10 nicotinic acetylcholine receptors (nAChRs) to calcium- activated SK potassium channels. The resulting hyperpolarization reduces OHC activity- evoked electromotility and is implicated in cochlear gain control, protection against acoustic trauma, and attention. MOC neurons also label for markers of GABA and GABA synthesis. GABAB autoreceptor (GABABR) activation on MOC terminals has been demonstrated to reduce ACh release, confirming important negative feedback roles. However, the full complement of GABAergic activity in the cochlea is not currently understood, including mechanisms of GABA release from MOC axons, whether GABA diffuses from MOC axons to other postsynaptic cells, and the location and function of GABAA receptors (GABAARs). We used optical neurotransmitter detection, immunohistochemistry, and patch- clamp electrophysiology to demonstrate that in addition to presynaptic GABAB autoreceptor activation, MOC efferent terminals release GABA onto type II SGN afferent dendrites with postsynaptic activity mediated by GABAARs. This synapse may have roles including developmental regulation of cochlear innervation, fine- tuning of OHC activity, or providing feedback to the brain about MOC and OHC activity.