State-dependent modulation of activity in distinct layer 6 corticothalamic neurons in barrel cortex of awake mice

Abstract

ABSTRACTLayer 6 corticothalamic (L6 CT) neurons are in a strategic position to control sensory input to the neocortex, yet we understand very little about their functions. Apart from studying their anatomical, physiological and synaptic properties, most recent efforts have focused on the activity-dependent influences CT cells can exert on thalamic and cortical neurons through causal optogenetic manipulations. However, few studies have attempted to study them during behavior. In an attempt to address this gap, we performed juxtacellular recordings from optogenetically identified CT neurons in whisker-related primary somatosensory cortex (wS1) of awake, head-fixed mice (of either sex) free to rest quietly or self-initiate bouts of whisking and locomotion. We found a rich diversity of response profiles exhibited by CT cells. Broadly, their spiking patterns were either modulated by whisker-related behavior (~28%) or not (~72%). Whisker-related neurons exhibited both increases as well as decreases in firing rates. We also encountered cells with preceding modulations in firing rate before whisking onset. Overall, whisking better explained these changes in rates than overall changes in arousal. The CT cells that showed no whisker-related activity had low spontaneous firing rates (<0.5 Hz), with many all but silent. Remarkably, this relatively silent population preferentially spiked at the state transition point when pupil diameter constricted and the mouse entered quiet wakefulness. Thus, our results demonstrate that L6 CT neurons in wS1 show diverse spiking patterns, perhaps subserving distinct functional roles related to precisely timed responses during complex behaviors and transitions between discrete waking states.