Complementary Ca2+ Activity of Sensory Activated and Suppressed Layer 6 Corticothalamic Neurons Reflects Behavioral State

Layer 6 (L6) corticothalamic neurons project to thalamus, where they are thought to regulate sensory information transmission to cortex. However, the activity of these neurons during different behavioral states has not been described. Here, we imaged calcium changes in visual cortex L6 primary corticothalamic neurons with two-photon microscopy in head-fixed mice in response to passive viewing during a range of behavioral states, from locomotion to sleep. In addition to a substantial fraction of quiet neurons, we found sensory-activated and suppressed neurons, comprising two functionally distinct L6 feedback channels. Quiet neurons could be dynamically recruited to one or another functional channel, and the opposite, functional neurons could become quiet under different stimulation conditions or behavior states. The state dependence of neuronal activity was heterogeneous with respect to locomotion or level of alertness, although the average activity was largest during highest vigilance within populations of functional neurons. Interestingly, complementary activity of these distinct populations kept the overall corticothalamic feedback relatively constant during any given behavioral state. Thereby, in addition to sensory and non-sensory information, a constant activity level characteristic of behavioral state is conveyed to thalamus, where it can regulate signal transmission from the periphery to cortex.