Layer 6 corticothalamic neurons show diverse and dynamic responses that support a role in cortical gain control in...

Listening in complex environments requires the enhancement of relevant sounds and suppression of irrelevant ones. Corticothalamic neurons (CTNs) in auditory cortex layer (L) 6 provide modulatory feedback to thalamic nuclei and to upper cortical layers and are thought to be involved in gain control. However, their role in auditory processing remains unclear. We used in vivo two-photon imaging in mice to investigate the responses of L6 CTNs during active and passive listening. During a tone-in-noise detection task with varying levels of difficulty, L6 CTN responses exhibited higher gain in hit than miss trials, and this gain increased with task difficulty, indicating the active role of L6 CTNs. During passive listening, L6 CTNs exhibited diverse receptive fields and a heterogeneous tonotopic organization, with responses either suppressed or facilitated by background noise. Together, our results reveal diverse and dynamic context-dependent responses of L6 CTNs, consistent with a role in gain control.