Layer 6 corticothalamic neurons induce high gamma oscillations through cortico-cortical and cortico-thalamo-cortical pathways

Layer 6 corticothalamic (L6CT) neurons are an excitatory neuron class with projections to both cortex and thalamus. L6CT neurons have been reported to induce multiple effects, including the up- and down-modulation of cortical and thalamic firing rates, and the enhancement of high gamma oscillations in the local field potential (LFP) of the surrounding cortex. These recently reported oscillations offer a neuronal substrate to link recurrent thalamocortical interactions, a critical connection hinging on L6CT neurons, to high frequency oscillations, that have been implicated in several cognitive and pathological conditions. We hypothesize that the high gamma oscillations induced by L6CT neurons in the cortex depend on the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this hypothesis, we optogenetically activated L6CT neurons in NTSR1-cre mice selectively expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway of awake, head-fixed mice, we presented LED ramp- and-hold inputs of different intensities while recording neuronal activity in the primary somatosensory barrel cortex (S1), the ventral posteromedial nucleus (VPm), and the reticular nucleus (TRN) of thalamus using silicon probes. First, we confirmed that the activation of L6CT neurons induces high-frequency oscillation of S1 local field potential. These oscillations are modulated in frequency, but not in amplitude, across LED intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the evolution over time of the firing rate of cortical neurons across layers and electrophysiologic cell classes, VPm, and TRN. While the firing rate of most cortical and TRN neurons was steadily suppressed over time, the firing rate of VPm and Layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to being facilitated within 500 ms. Using dimensionality reduction, we found that this pattern reflects two underlying components: one stable component that is represented across all units, and one evolving component that is mainly represented in VPm and in L4 FS neurons, suggestive of differential recruitment of the cortico-cortical vs cortico-thalamo-cortical pathways. Finally, we related the firing rate of each unit to the amplitude and frequency of S1 LFP, finding that the evolution of S1 LFP amplitude weakly correlates with all neurons, while its frequency selectively correlates with VPm firing rate. Taken together, our data suggests that L6CT neurons generate high gamma oscillations in S1 LFP through a combination of intracortical and cortico-thalamo-cortical pathways and can sculpt its oscillation frequency through the cortico-thalamo-cortical pathway. Our findings provide a neuronal substrate for linking recurrent interactions, mediated by L6CT neurons, to the modulations of high gamma oscillations observed in several brain states and pathological conditions.