Strength of the efferent olivocochlear system modifies the activity of a central auditory nuclei.

DI GUILMI, MN; GÓMEZ CASATI, ME; BOERO, L; ELGOYHEN, AB

Congreso; ARO midwinter meeting; 2016

The auditory system in many mammals is immature at birth but precisely organized inadults. Spontaneous activity in the inner ear comes into play to guide this process. Thisspontaneous activity is modulated by an efferent pathway that descends from the brain(Walsh et al., 1998). In the medial nucleus of the trapezoid body (MNTB), neurons aretopographically organized along a medio-lateral axis with the most medially locatedcells responding to high frequencies, changing to lower characteristic frequencies in themost lateral cells. The specific aim of this work is to understand the role of the medialolivocochlear (MOC) system in the correct establishment of the MNTB tonotopy.We used mice with enhanced MOC activity (Chrna9L9?T, knock-in, KI) in which theα9 nicotinic receptor subunit bears a point mutation that leads to a gain of function(Taranda et al., 2009). Auditory brainstem responses (ABR) at P21 andelectrophysiological recordings between P12-14 (patch-clamp, whole-cellconfiguration) on brainstem slices containing the MNTB were evaluated. Both currentand voltage-clamp configurations were performed in order to study the tonotopy of theMNTB.Wave I amplitude of the ABR was the same for WT and KI mice at 8, 16 and 32 KHz.However, there was a reduction in the amplitude of wave III in KI mice that was largerat high frequencies (~ 23% reduction at 16 KHz and 35% at 32 KHz). Theseobservations suggest a central dysfunction. In order to analyze in depth these functionalobservations and focus on tonotopy, we studied the MNTB nucleus. Under currentclampmode, while medial MNTB neurons in WT showed a more depolarizedmembrane potential and a larger membrane resistance than lateral ones; both propertieswere not tonotopically distributed in KI mice. Additionally, medio-lateral actionpotential firing differences after a depolarized current pulse injection observed in WT(medial: 201±11 Hz; lateral: 153±18 Hz; p=0.03) were absent in KI mice medial:182±14 Hz; lateral: 155±10 Hz, p>0.05). Under voltage-clamp mode, Ih current waslarger in medial compared to lateral cells in WT. However, this tonotopic differencewas reduced in KI animals.These results suggest that medial efferent activity before hearing onset is involved in therefinement of the tonotopic map of the MNTB.