Activation and inhibition of corticothalamic feedback on network state
Principal cells of cortical layer 6 (L6) provide an excitatory modulatory projection to the primary thalamic nuclei, the function of which is still questioned. Previously we proved that the activation of these layer 6 cells might be able to change on-going network state, locally. In the present study we tested if the specific inhibition of them can induce a state change in the thalamocortical system. We used chronically implanted NTSR1-Cre transgenic mice, in which thalamically projecting layer 6 neurons selectively express hM4 or eNpHR3 due to viral transfection. Cortical local field was measured while layer 6 neurons were chemogenetically or optogenetically inhibited, respectively.In a previous study, we were able to suppress spindling activity of primary somatosensory cortex using mild excitation of L6 cells via ChR2 activation or induce desynchronization by stronger excitation of L6 pyramidal neurons. Chemogenetic inhibition of L6 was induced by the intraperitoneal injection of clozapine-N-oxid (CNO). When no other stimulation was applied, CNO had no effect on spontaneous network activity, the pattern of natural sleep or the number of sleep spindles remained unaffected. When CNO was administered to NTSR1-ChR2 expressing animals, it partially antagonized the excitatory effect of ChR2 activation, the sleep spindle suppression and desynchronization inducing effects were not so pronounced. Optogenetic inhibition of layer 6 cells have mild effect, in stage II sleep spindles were hardly suppressed. We conclude that corticothalamic feedback can indeed act as a local modulator in the thalamocortical system.