Thalamic Drive of Cortical Parvalbumin-Positive Interneurons during Down States in Anesthetized Mice

Up and down states are among the most prominent features of the thalamo-cortical system during non-rapid eye movement (NREM) sleep and many forms of anesthesia. Cortical interneurons, including parvalbumin (PV) cells, display firing activity during cortical down states, and this GABAergic signaling is associated with prolonged down-state durations. However, what drives PV interneurons to fire during down states remains unclear. We here tested the hypothesis that background thalamic activity may lead to suprathreshold activation of PV cells during down states. To this aim, we performed two-photon guided juxtasomal recordings from PV interneurons in the barrel field of the somatosensory cortex (S1bf) of anesthetized mice, while simultaneously collecting the local field potential (LFP) in S1bf and the multi-unit activity (MUA) in the ventral posteromedial (VPM) thalamic nucleus. We found that activity in the VPM was associated with longer down-state duration in S1bf and that down states displaying PV cell firing were associated with increased VPM activity. Moreover, thalamic inhibition through application of muscimol reduced the fraction of spikes discharged by PV cells during cortical down states. Finally, we inhibited PV interneurons using optogenetics during down states while monitoring cortical LFP under control conditions and after thalamic muscimol injection. We found increased latency of the optogenetically triggered down-to-up transitions upon thalamic pharmacological blockade compared to controls. These findings demonstrate that spontaneous thalamic activity inhibits cortex during down states through the activation of PV interneurons. [Display omitted] •Thalamic activity in VPM is associated with longer down states in S1bf•Thalamic inactivation decreases spikes of PV cells in S1bf during down states•Thalamic suppression delays network response to PV cell silencing in down states•Thalamus suppresses S1bf during down states through activation of PV cells Using a combination of electrophysiology, local pharmacology, and cell-specific optogenetic perturbations, Zucca et al. provide evidence that spontaneous thalamic activity inhibits cortex during down states through the suprathreshold activation of PV-positive interneurons.