Synaptic Mechanisms of Top-Down Control in the Non-Lemniscal Inferior Colliculus

Abstract

Corticofugal projections to evolutionarily ancient, sub-cortical structures are ubiquitous across mammalian sensory systems. These descending pathways enable the neocortex to control ascending sensory representations in a predictive or feedback manner, but the underlying cellular mechanisms are poorly understood. Here we combine optogenetic approaches with in vivo and in vitro patch-clamp electrophysiology to study the projection from auditory cortex to the inferior colliculus (IC), a major descending auditory pathway that controls IC neuron feature selectivity, plasticity and auditory perceptual learning. Although individual auditory cortico-collicular synapses were generally weak, IC neurons often integrated inputs from multiple corticofugal axons that generated reliable, tonic depolarizations even during prolonged presynaptic activity. Latency measurements in vivo showed that descending signals reach the IC within 30 ms of sound onset, which in IC neurons corresponded to the peak of synaptic depolarizations evoked by short sounds. Activating ascending and descending pathways at latencies expected in vivo caused a NMDA receptor dependent, supra-linear EPSP summation, indicating that descending signals can non-linearly amplify moment-to-moment acoustic responses. Our results shed light upon the synaptic bases of descending sensory control, and imply that heterosynaptic cooperativity contributes to sub-cortical plasticity and perceptual learning.

Evidence for Layer-Specific Connectional Heterogeneity in the Mouse Auditory Corticocollicular System

“…Thus, these corticocollicular neurons may be the main mediators of frequency shifts and changes in duration tuning observed in the IC-on-AC stimulation. The presence of direct thalamocortical connections onto layer 5 corticocollicular cells (Slater et al, 2019), coupled with their tendency to fire in bursts (Slater et al, 2013), and the presence of large, depressing, AMPA-mediated EPSCs in presumed layer 5 corticocollicular synapses (Oberle et al, 2021), now combined with the finding of large synaptic connections, suggest that layer 5 corticocollicular cells can have rapid, powerful, and frequency-specific effects on IC neurons, similar to "drivers" that have been described in the layer 5 corticothalamic system (Sherman and Guillery, 2011).…”