Central auditory synapse alterations in mice with enhanced and suppressed medial olivocochlear efferent activity

CHEQUER CHARAN, D; HUANG, W; GOMEZ CASATI, ME; HUA, Y; ELGOYHEN, AB; DI GUILMI, MN

Congreso; Congreso anual de la Sociedad de Neurociencias; 2023

Spontaneous activity in the immature inner ear plays a critical role in the development of precise connectivity in the central auditory system. This is modulated by the medial olivocochlear system (MOC). In mice with enhanced MOC activity (KI), synaptic dysfunctions were observed in the medial nucleus of the trapezoid body (MNTB) (Di Guilmi et al., 2019). In the present work, we performed electrophysiological recordings and morphological 3D reconstructions of the calyx of Held (CH)-MNTB synapse at P12-14 in three mouse models: WT, KI and KO (which lacks MOC activity). Short term synaptic plasticity (STP) experiments displayed a significant higher rate of depression in the KI than WT and KO (10Hz; ??WT=2.99±0.21s, ??KI=1.96±0.24s, ??KO=3.42±0.56s, n=16, ANOVA, p=0,001; 100Hz; ??WT=4.89±2.42s, ??KI=2.32±0.98s, ??KO=7.09±1.58s, n=16, ANOVA, p=0.013). Morphological analysis of CHs in WT and KI mice by volumetric reconstructions from serial electron microscopy images at P25 showed that the KI has a lower proportion of complex CHs compared to WT (69% vs. 83%). Considering that the CH morphology determines the STP, the larger depression rate in the KI aligns with the observation that principal MNTB neurons receive innervation from CHs with simple morphologies (Grande & Wang, 2011). The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period is involved in setting the correct synaptic transmission at central auditory nuclei.