GABA and ACh are co-transmitted from olivocochlear efferent terminals during development

TAIS CASTAGNOLA; VALERIA C. CASTAGNA; MARIA EUGENIA GÓMEZ CASATI; ANA BELÉN ELGOYHEN; ELEONORA KATZ; JUAN GOUTMAN; CAROLINA WEDEMEYER

San Luis

Congreso; XXXVIII Reunión Anual de la SAN; 2023

Sociendad Argentina de Investigaciones en Neurociencias (SAN)

During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but fire sensory-independent action potentials, crucial for the normal development of the auditory pathway. During this period, neurons from the medial olivocochlear complex (MOC) transiently innervate IHCs. This innervation is mediated by acetylcholine (ACh), activating nicotinic receptors α9α10 and is responsible for controlling IHC excitability during this period. Even though this is a cholinergic synapse, GABA through presynaptic GABAB receptors reduces the amount of ACh released. While we described the GABA-mediated mechanisms, the source of GABA and the role of GABAergic modulation are poorly understood. Using mice expressing channelrodhopsin (ChR2) under the control of either GAD or ChAT promoters we show that optogenetically activated fibers in GAD-cre/ChR2 mice produced postsynaptic responses that were blocked with cholinergic antagonists. Finally, calcium imaging experiments were performed with stimulation of MOC fibers, allowing us to resolve the activation of single synaptic sites. Altogether these results strongly suggest that ACh is being co-transmitted with GABA from MOC fibers. Whereas ACh acts postsynaptically activating α9α10 receptors, the role of GABA is presynaptic, as a negative feedback signal to locally regulate cholinergic inhibition of IHCs. Calcium imaging experiments suggest that GABA modulation operates differently at each synaptic site.