Inhibitory NPY neurons provide a large and heterotopic commissural projection in the inferior colliculus

Abstract

Located in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The right and left side of the IC are interconnected by a dense fiber tract, the commissure of the IC (CoIC), that provides each IC with one its largest sources of input (i.e., the contralateral IC). Despite its prominence, the CoIC remains poorly understood. Previous studies using anterograde and retrograde tract-tracing showed that IC commissural projections are predominately homotopic and tonotopic, targeting mirror-image locations in the same frequency region in the contralateral IC. However, it is unknown whether specific classes of neurons, particularly inhibitory neurons which constitute ~10-40% of the commissural projection, follow this pattern. We therefore examined the commissural projections of Neuropeptide Y (NPY) neurons, the first molecularly identifiable class of GABAergic neurons in the IC. Using retrograde tracing with Retrobeads in NPY-hrGFP mice of both sexes, we found that NPY neurons comprise ~11% of the commissural projection. Moreover, focal injections of Retrobeads showed that NPY neurons in the central nucleus of the IC exhibit a more divergent and heterotopic commissural projection pattern than non-NPY neurons. Thus, commissural NPY neurons are positioned to provide cross-frequency, lateral inhibition to the contralateral IC. Through this circuit, sounds that drive activity in limited frequency bands on one side of the IC might suppress activity across a larger number of frequency bands in the contralateral IC.

Cholinergic boutons are distributed along the dendrites and somata of VIP neurons in the inferior colliculus

“…For each analyzed section, a tile-scan image of one side of the IC was collected using a 20× objective. The borders of the ICc were delineated following the approach developed by Choy Buentello et al (2015), for which we used an atlas of anti-GAD67 and anti-GlyT2-stained IC sections prepared for a previous study from our lab (Anair et al 2022). Regions of interest from the ICc that contained one or more VIP neuron somata were then chosen for analysis by examining only the tdTomato fluorescence channel (i.e., the VIP neuron channel); immunofluorescence from the VAChT channel was not visualized during the neuron selection process to avoid biasing results.…”