"The efferent olivocochlear system and development of the central auditory circuit"

ELGOYHEN AB

Congreso; 2nd Shanghai Forum on the Frontier of Hearing Research and 2019 Shanghai Institute of Precision Medicine Symposium; 2019

The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear comes into play to guide this process. This spontaneous activity is modulated by an efferent pathway that descends from the brain (1). In this work, we used a mouse model with enhanced medial efferent activity (Chrna9L9?T, KI) (2) to understand the role of the olivocochlear efferent system in the correct establishment of auditory circuits. We measured auditory brainstem responses (ABR), which represents synchronized activity of neurons along the auditory pathway. As was previously shown, ABR thresholds were elevated in the KI (2). Wave I amplitude (activity of cochlear nerve fibers) was the same for WT and KI. However, wave III (activity of synapses within the MNTB) was smaller in the KI suggesting a central dysfunction. Furthermore, this difference was larger at high frequencies. In order to analyze this functional observation, we studied the underlying mechanism on brain slices containing the medial nucleus of the trapezoid body (MNTB) where neurons are topographically organized along a medio-lateral axis. The most medially located cells respond to high frequencies, changing to lower characteristic frequencies in the most lateral cells. Under voltage-clamp mode, hyperpolarization-activated potassium currents (Ih) were larger in medial compared to lateral cells in WT, in agreement with a previous observation (3). However, this tonotopic difference was reduced in the KI. Furthermore, the number of spikes during a current pulse injection was larger in medial than in lateral MNTB for WT. Notably, this difference was abolished in the KI. Our preliminary results suggest that the efferent pathway could be involved in the refinement of the tonotopic map along the auditory pathway, ensuring the presence of high frequency coding cells. (1. Kotak and Sanes, 1995; 2. Taranda et al., 2009; 3. Leao et al., 2006).