Strengthening of the efferent olivocochlear system leads to synaptic dysfunction and tonotopy disruption of a central auditory nucleus

BOERO, LUIS E.; ELGOYHEN, ANA BELÉN; GÓMEZ-CASATI, MARÍA EUGENIA; RODRÍGUEZ-CONTRERAS, ADRIÁN; DI GUILMI, MARIANO N.; WEDEMEYER, CAROLINA

Caba

Workshop; IHeaR; 2019

The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner earplays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makestransient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an α9 cholinergic receptor knock-in mousemodel (of either sex) with enhanced medial efferent activity (Chrna9L9′T, L9′T) to understand the role of the olivocochlear systemin the correct establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activityof synapses within the superior olivary complex) were smaller in L9′T mice, suggesting a central dysfunction. The mechanismunderlying this functional alteration was analysed in brain slices containing the medial nucleus of the trapezoid body (MNTB),where neurons are topographically organized along a medio-lateral axis. The topographic organization of MNTB physiologicalproperties observed in WT mice was abolished in the L9′T mice. Additionally, electrophysiological recordings in slices evidencedMNTB synaptic alterations, which were further supported by morphological alterations. The present results suggest that thetransient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement oftopographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.