Inhibitory Projections from the Inferior Colliculus to the Medial Geniculate body Originate from Four Subtypes of GABAergic Cells.

N L Beebe,J G Mellott,B R Schofield

doi:10.1523/eneuro.0406-18.2018

Abstract

GABAergic cells constitute 20–40% of the cells that project from the inferior colliculus [(IC) a midbrain auditory hub] to the medial geniculate body [(MG) the main auditory nucleus of the thalamus]. Four subtypes of GABAergic IC cells have been identified based on their association with perineuronal nets (PNs) and dense rings of axosomatic terminals expressing vesicular glutamate transporter 2 (VGLUT2 rings). These subtypes differ in their soma size and distribution within the IC. Based on previous work emphasizing large GABAergic cells as the origin of GABAergic IC–MG projections, we hypothesized that GABAergic IC cells surrounded by PNs and VGLUT2 rings, which tend to have larger somas, were more likely to project to the MG than smaller cells lacking these extracellular markers. Here, we injected retrograde tract tracers into the MG of guinea pigs of either sex and analyzed retrogradely labeled GABAergic cells in the ipsilateral IC for soma size and association with PNs and/or VGLUT2 rings. We found a range of GABAergic soma sizes present within the IC–MG pathway, which were reflective of the full range of GABAergic soma sizes present within the IC. Further, we found that all four subtypes of GABAergic IC cells participate in the IC–MG pathway, and that GABAergic cells lacking PNs and VGLUT2 rings were more prevalent within the pathway than would be expected based on their overall prevalence in the IC. These results may provide an anatomical substrate for the multiple roles of inhibition in the IC–MG pathway, which have emerged in electrophysiological studies.

Highlights

Throughout sensory systems, GABAergic cells often make only local projections, defining them as interneurons
Based on previous work emphasizing large GABAergic cells as the origin of GABAergic inferior colliculus (IC)–MG projections, we hypothesized that GABAergic IC cells surrounded by perineuronal nets (PNs) and vesicular glutamate transporter 2 (VGLUT2) rings, which tend to have larger somas, were more likely to project to the MG than smaller cells lacking these extracellular markers
We found that all four subtypes of GABAergic IC cells participate in the IC–MG pathway, and that GABAergic cells lacking PNs and VGLUT2 rings were more prevalent within the pathway than would be expected based on their overall prevalence in the IC

Summary

Introduction

Throughout sensory systems, GABAergic cells often make only local projections, defining them as interneurons. A previous study describes the inhibitory component of the IC–MG pathway as dominated by large GABAergic (LG) neurons with somas larger than 16.5 ␮m in diameter and dense axosomatic input from terminals containing vesicular glutamate transporter 2 (VGLUT2; Ito et al, 2009). The other subtype, small GABAergic (SG) cells, have somas smaller than 10.7 ␮m in diameter, do not receive axosomatic VGLUT2-containing terminals, and are unlikely to project to the MG (Ito et al, 2009). The authors suggest that the large size coupled with dense axosomatic inputs from excitatory terminals allow LG cells to provide short latency inhibition that arrives in the MG before excitation (Peruzzi et al, 1997; Ito and Oliver, 2012). Many studies find a range of latencies for IC-generated inhibition in the MG, and an IC–MG pathway dominated by inhibition from LG cells is difficult to reconcile with these physiologic data (Hu et al, 1994; Bartlett and Smith, 1999)

Methods

Results

Discussion

Conclusion