The role of feedback from the auditory cortex in shaping responses to sounds in inferior colliculus

Abstract The extensive feedback from the auditory cortex (AC) to the inferior colliculus (IC) supports critical aspects of auditory learning, but has not been extensively characterized. Furthermore, it remains unknown whether and how intra-cortical processing of auditory information propagates to earlier stages in the auditory pathway. Previous studies demonstrated that responses of neurons in IC are altered by focal electrical stimulation and pharmacological inactivation of auditory cortex, but these methods lack the ability to selectively manipulate the activity of projection neurons. Combining viral technology with electrophysiological recordings, we measured the effects of selective optogenetic activation or suppression of cortico-collicular feedback projections on IC responses to sounds. Activation of cortico-collicular feedback generally increased spontaneous activity and decreased stimulus selectivity in IC, whereas suppression of the feedback did not affect collicular activity. To further understand how microcircuits in the auditory cortex may control collicular activity, we tested the effects of optogenetically modulating different cortical neuronal subtypes, specifically parvalbumin-positive (PV) and somatostatin-positive (SOM) inhibitory interneurons. We found that, despite strong effects on sound-evoked responses across the layers of AC, activating either type of interneuron did not affect IC sound-evoked activity. However, suppression of SOMs, but not PVs, weakly increased spontaneous activity in IC. These findings suggest that shaping of sound responses mediated by cortical inhibition does not affect sound processing in IC. Combined, our results identify that activation of excitatory projections, but not inhibitory-driven increases in cortical activity, affects collicular sound responses. Significance Statement Descending projections from the auditory cortex to the auditory midbrain, the inferior colliculus, have been shown to play a critical role in auditory learning and behavior. However, little is known about the details of how this direct feedback shapes neuronal responses to sounds in the inferior colliculus. We found that direct activation of cortico-collicular feedback increased spontaneous and modulated sound-evoked activity in the inferior colliculus. Interestingly, modulation of inhibitory interneuron activity, thereby increasing or decreasing excitatory neuronal activity in the auditory cortex, did not affect sound responses in the inferior colliculus. This work offers evidence that auditory cortex shapes sound responses in the inferior colliculus via direct feedback independently of the activity of cortical inhibitory interneurons.