GABAergic modulation of the efferent cholinergic innervation in the developing cochlea. Where does GABA come from??

JUAN DIEGO GOUTMAN; TAIS CASTAGNOLA ; CAROLINA WEDEMEYER; ANA BELEN ELGOYHEN

Villa Carlos Paz, Cordoba

Congreso; XXXIV Annual Meeting of the Argentinian Society of Neuroscience; 2019

Sociedad Argentina de Neurociencia

During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead present intrinsic electrical activity, crucial for the normal development of the auditory pathway. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs. This innervation is mediated by acetylcholine (ACh), activating nicotinic receptors assembled by α9 and α10 subunits and is responsible for controlling IHC excitability during this period. Even though this is a cholinergic synapse, previous evidence indicates the presence of abundant GABA and presynaptic GABAB receptors. Moreover, the application of GABAB receptors agonists can reduce ACh release. To determine the source of GABA in the MOC ? IHC synapse, transgenic mice expressing channelrodhopsin (ChR2) in GABAergic fibers were used. Preliminary results indicate that ChR2 activation by light did not elicit any measurable synaptic response in IHC per se, but produced a transient potentiation of cholinergic synaptic responses (when coupled with an electrical stimulation) in 10/28 cases. In addition, immunohistochemistry techniques were used to characterize GABA innervation. On the other hand, to further understand the mechanisms of GABA modulation we used calcium imaging techniques that allowed us to estimate activity at a single synapse level. Altogether these results suggest that ACh might be released from fibers that have a GABAergic identity.