Recurrent circuits amplify corticofugal signals and drive feed-forward inhibition in the inferior colliculus

Abstract

AbstractThe inferior colliculus (IC) is a midbrain hub critical for perceiving complex, time-varying sounds such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending inputs from auditory cortex that control IC neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although these corticofugal synapses primarily release the excitatory transmitter glutamate, many physiology studies show that auditory cortical activity has a net inhibitory effect on IC neuron spiking. Perplexingly, anatomy studies indicate that corticofugal axons primarily target glutamatergic IC neurons while only sparsely innervating IC GABA neurons, thereby suggesting that corticofugal inhibition of the IC occurs largely independently of feedforward activation of local GABA neurons. We shed light on this paradox using in vitro electrophysiology and optogenetics in acute IC slices from fluorescent reporter mice. We find that corticofugal synaptic strength is indeed stronger onto IC glutamate compared to GABA neurons. Nevertheless, two mechanisms enable reliable corticofugal activation of local GABA neurons. 1) Many IC GABA neurons fire tonically at rest, such that sparse and weak excitation suffices to significantly increase their spike rates. 2) Corticofugal activity triggers barrages of large amplitude, polysynaptic EPSPs in IC GABA neurons, owing to a dense intra-collicular connectivity from local axon collaterals of IC glutamate neurons. Consequently, repetitive activity in corticofugal fibers drives spikes in IC GABA neurons and generates substantial recurrent inhibition. Thus, descending signals trigger intra-collicular inhibition despite apparent constraints of monosynaptic connectivity between auditory cortex and IC GABA neurons.