Development
Author: Daniela Maria Chequer Charan | Email: danichch92@gmail.com
Daniela Maria Chequer Charan1°, Wenqing Huang2°,María Eugenia Gómez-Casati3°, Carolina Wedemeyer1°, Yunfeng Hua2°, Ana Belén Elgoyhen1°, Mariano Nicolas Di Guilmi1°
1° Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI), Laboratorio de Fisiología y Genética de la Audición, Buenos Aires, Argentina
2° Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Shanghai Institute of Precision Medicine, Shanghai, China
3° Instituto de Farmacología, Facultad de Medicina. Universidad de Buenos Aires. Argentin
In many mammals, the auditory system is immature at birth but fine-tuned in adults. The activity of medial olivocochlear system (MOC) leads to an accurate development of precise central connectivity by modulating spontaneous activity in the immature inner ear. In mice with enhanced MOC activity (KI), synaptic dysfunction of calyx of Held (CH) in the medial nucleus of the trapezoid body (MNTB) have been observed at different developmental stages (Di Guilmi et al., 2019). In this work, we set out a physiological and structural investigation of the CH-type synapses from electrophysiological recordings at P12-14 and morphological 3D reconstructions at P25 in three mouse models: WT, KI and KO (which lacks MOC activity). The KI displayed lower excitatory postsynaptic current amplitude than WT (WT:4,73±0,37nA, n=21, KI:3,74±0,27nA, n=20, KO:4,18±0,30nA, n=19, ANOVA, p=0.02) and it showed higher short term depression (STD) at low (10Hz) and high (100Hz and 300Hz) frequency stimulus. The 3D-reconstruction of the P25 CH-MNTB from serial-block electron microscopy (SBEM) indicates that a lower proportion of morphologically complex CHs and synaptic pruning are found in the KI model (KI=69% vs. WT=83%). This results in addition with the relation reported by Grande & Wang, 2011 where CH morphology correlates with the STD, allow us to conclude that enhancing the MOC activity triggers deeper developmental changes in comparison with a model without MOC modulation.