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

Articulo

Authorship:

Julia L. Bachman ; Siân R. Kitchera ; Lucas G. Vattino ; Holly J. Beaulaca ; M. Grace Chavesa ; Israel Hernandez Rivera ; KATZ, ELEONORA ; Carolina Wedemeyer ; Catherine J. C. Weisz

Date:

2025

Publishing House and Editing Place:

NATL ACAD SCIENCES

Magazine:

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 122 NATL ACAD SCIENCES

Summary *

Cochlear outer hair cells (OHCs) are electromotile and implicated in amplification ofresponses to sound that enhance sound sensitivity and frequency tuning. They sendafferent information through glutamatergic synapses onto type II spiral ganglionneurons (SGNs). These synapses are weaker than those from cochlear inner hair cellsonto 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 ofalpha9/alpha10 nicotinic acetylcholine receptors (nAChRs) to calcium- activated SKpotassium channels. The resulting hyperpolarization reduces OHC activity- evokedelectromotility and is implicated in cochlear gain control, protection against acoustictrauma, and attention. MOC neurons also label for markers of GABA and GABAsynthesis. GABAB autoreceptor (GABABR) activation on MOC terminals has beendemonstrated to reduce ACh release, confirming important negative feedback roles.However, the full complement of GABAergic activity in the cochlea is not currentlyunderstood, including mechanisms of GABA release from MOC axons, whether GABAdiffuses from MOC axons to other postsynaptic cells, and the location and functionof GABAA receptors (GABAARs). We used optical neurotransmitter detection, immunohistochemistry, and patch- clamp electrophysiology to demonstrate that in additionto presynaptic GABAB autoreceptor activation, MOC efferent terminals release GABAonto 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 MOCand OHC activity Information provided by the agent in SIGEVA

Key Words

GAMMA-AMINOBUTYRIC ACID (GABA)MEDIAL OLIVOCOCHLEAR (MOC)AUDITORYSYNAPSESPIRAL GANGLION NEURON (SGN)