Strengthening of the Efferent Olivocochlear System Leads to Synaptic Dysfunction and Tonotopy Disruption of a Central Auditory Nucleus

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

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2019 vol. 39 p. 7037 - 7048

0270-6474

The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear playsa critical role in guiding this maturation process. This is shaped by an efferent pathway that descends from the brainstem and makestransient direct synaptic contacts with inner hair cells. In this work, we used an9 cholinergic nicotinic receptor knock-in mouse model(of either sex) with enhanced medial efferent activity (Chrna9L9T, L9T) to further understand the role of the olivocochlear system in thecorrect establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activity of synapseswithin the superior olivary complex) was smaller in L9T mice, suggesting a central dysfunction. The mechanism underlying thisfunctional alteration was analyzed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons aretopographically organized along a mediolateral (ML) axis. The topographic organization of MNTB physiological properties observed inwildtype (WT) was abolished in L9T mice. Additionally, electrophysiological recordings in slices indicated MNTB synaptic alterations.In vivo multielectrode recordings showed that the overall level ofMNTBactivity was reduced in the L9T. The present results indicate thatthe transient cochlear efferent innervation to inner hair cells during the critical period before the onset of hearing is involved in therefinement of topographic maps as well as in setting the properties of synaptic transmission at a central auditory nucleus.