TY - JOUR T1 - Strengthening of the efferent olivocochlear system leads to synaptic dysfunction and tonotopy disruption of a central auditory nucleus JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.2536-18.2019 SP - 2536-18 AU - Mariano N. Di Guilmi AU - Luis E. Boero AU - Valeria C. Castagna AU - Adrián Rodríguez-Contreras AU - Carolina Wedemeyer AU - María Eugenia Gómez-Casati AU - Ana Belén Elgoyhen Y1 - 2019/06/19 UR - http://www.jneurosci.org/content/early/2019/06/19/JNEUROSCI.2536-18.2019.abstract N2 - The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this maturation process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an α9 cholinergic nicotinic receptor knock-in mouse model (of either sex) with enhanced medial efferent activity (Chrna9L9′T, L9′T) to further understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activity of synapses within the superior olivary complex) was smaller in L9′T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analyzed 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 physiological properties observed in WT was abolished in L9′T mice. Additionally, electrophysiological recordings in slices indicated MNTB synaptic alterations. In vivo multielectrode recordings showed that the overall level of MNTB activity was reduced in the L9′T. The present results indicate that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the properties of synaptic transmission at a central auditory nucleus.SIGNIFICANCE STATEMENTCochlear inner hair cells of altricial mammals display spontaneous electrical activity before hearing onset. The pattern and firing rate of these cells are crucial for the correct maturation of the central auditory pathway. A descending efferent innervation from the central nervous system contacts the hair cells during this developmental window. The present work shows that genetic enhancement of efferent function disrupts the orderly topographic distribution of biophysical and synaptic properties in the auditory brainstem and causes severe synaptic dysfunction. This work adds to the notion that the transient efferent innervation to the cochlea is necessary for the correct establishment of the central auditory circuitry. ER -