The medial efferent system during development of the auditory pathway

CASTAGNA, VC; BOERO, L; ELGOYHEN, AB; GÓMEZ CASATI, ME

Carlos Paz

Congreso; Congreso de la Sociedad Argentina de Neurociencias; 2019

The auditory system of many mammals develops after birth. A fundamental question in development neuroscience is what processes are involved. It has been described that before the onset of hearing inner hair cells (IHCs) of the cochlea are innervated by neurons of the afferent system and transiently by neurons of the medial olivocochlear system. During this period, IHC exhibit periodic depolarization patterns, generating Ca+2 action potentials that produce the release of glutamate. These events induce stereotyped bursts of action potentials that are transmitted to the auditory circuits in the brain and promote neuronal survival, physiological maturation, and the proper establishment of the tonotopic map. The transient efferent innervation to IHCs of the cochlea has been proposed as a modulator of this activity. It has been shown that animals with alterations in this system have disruptions of functions in adult stages. In this work we sought to understand the function of this transient synapse during the critical period of the beginning of hearing. We used a previously reported genetically modified mice carrying an α9 cholinergic receptor subunit point mutation that leads to enhanced responses to medial olivocochlear activity. First, we analyze the onset of hearing in mice with enhanced medial olivocochlear function. We found that these knock-in gain of function animals start to hear a day before than wild types, which means that the efferent system might be involved in cochlear development. Second, we observed that the maturation of the auditory system is a process that occurs from the periphery towards the higher nuclei and it occurs at different periods. Finally, we evidenced that afferent synapse formation begins as a multiple innervation, where each inner hair cell is contacted by many afferent axons. At the onset of hearing, a "prune" and refinement of these synapses occurs until the average number of contacts present in the adults is reached.