Strength of the efferent olivocochlear system modify the normal activity of a central auditory nuclei

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

Rio de Janeiro

Congreso; 9th World Congress International Brain Research Organization; 2015

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. In the medial nucleus of the trapezoid body (MNTB), neurons are topographically organized along a medio-lateral axis with the most medially located cells responding to high frequencies, changing to lower characteristic frequencies in the most lateral cells. The specific aim of this work is to understand the role of the olivocochlear efferent system in the correct establishment of auditory circuits. We used a murine model with enhanced medial efferent activity, the Chrna9L9T knock-in (KI), a mouse in which the alpha9 nicotinic receptor subunit bears a point mutation that leads to a gain of function. First, 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 (Taranda et al., 2009). Interestingly, wave I amplitude (activity of cochlear nerve fibers) was the same for WT and KI (WT: 0.51 ± 0.04 μV; KI: 0.55 ± 0.04 μV at 16 and KHz WT: 0.52 ± 0.04 μV; KI: 0.50 ± 0.03 μV at 32 KHz). However, the amplitude of wave III (activity of synapses within the MNTB) was smaller in the KI mouse, suggesting a central dysfunction (WT: 1.12 ± 0.06 μV; KI: 0.86 ± 0.05 μV at 16 KHz and WT: 0.74 ± 0.06 μV; KI: 0.48 ± 0.05 μV at 32 KHz) . Furthermore, this difference was larger at high frequencies. In order to analyze in depth this functional observation, we decided to study the underlying mechanism at the level of slices containing the MNTB. 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 (Leao et al., 2006). However, this tonotopic difference was reduced in the KI. Under current-clamp mode, the number of spikes during a current pulse injection was larger in the medial than in the lateral MNTB for WT. Notably, this tonotopic difference was abolished in the KI. These 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.