GABA modulation of olivocochlear efferent neurotransmission

A. BELEN ELGOYHEN; TAIS CASTAGNOLA; CAROLINA WEDEMEYER; JUAN D. GOUTMAN

Simposio; International Hearing Research Symposium iHear 2019; 2019

During a critical developmental period, cochlear inner hair cells (IHCs) fire sensory-independent action potentials, crucial for the normal development of the auditory pathway. During this same period, neurons originating at the medial olivochlear complex (MOC) transiently innervate IHCs. This innervation is mediated by acetylcholine (ACh), activating nicotinic receptors assembled by alpha9 and alpha10 subunits. These receptors present an unusually high Ca2+ permeability, allowing relatively high amounts of this cation in IHC once activated. However, the synapse between MOC fibers and IHC is inhibitory because Ca2+ influx is coupled to the activation of a Ca2+-dependent K+ conductance, SK2, producing an overal inhibition in IHC. The MOC innervation has been shown to be critical for the control of IHC excitability during development. Even though ACh is the main neurotransmitter at this synapse, an abundant GABA innervation is also present. In a recent work we described that activation of MOC efferent fibers triggers the release of ACh, that can also be modulated by presynaptic GABAB receptors, reduicng the amount of ACh release. Although we described the GABA-mediated mechanisms at this synapse, the source of GABA and the role of GABAergic modulation at this critical period are poorly understood. In the present work, transgenic mice expressing channelrhodopsin (ChR2) in cholinergic (Chat tm2(crc)Lowl/J x ChR2) or in GABAergic (GAD2 tm1(cre/ERT2)Zjh/J x ChR2) fibers are used to elucidate whether GABA is co-released from cholinergic MOC terminals, or if alternatively, specialized GABAergic fibers project to the IHC inner spiral plexus.