Abstract
SummaryUp 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.
Highlights
Cortical interneurons, including parvalbumin (PV) cells, display firing activity during cortical down states, and this GABAergic signaling is associated with prolonged down-state durations
We found that activity in the ventral posteromedial (VPM) was associated with longer down-state duration in S1bf and that down states displaying PV cell firing were associated with increased VPM activity
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
Summary
Viral Injections The adeno-associated virus AAV1.CBA.Flex.Arch-GFP.WPRE.SV40 (Arch) was purchased from the University of Pennsylvania Viral Vector Core. PV-Cre transgenic mice (both males and females) were injected between postnatal day 0 (P0) and P2. Pups were anesthetized using hypothermia, placed on a custom-made stereotaxic apparatus and kept at approximately 4C for the entire duration of Current Biology 29, 1481–1490.e1–e6, May 6, 2019 e1 the surgery. A small skin incision was used to expose the skull and $250 nL of viral suspension were injected using a micropipette at stereotaxic coordinates of 0 mm from bregma, 2 mm lateral of the sagittal sinus, and 0.25–0.3 mm depth. The micropipette was held in place for 1–2 min before retraction. The skin was sutured, and the pup was revitalized under an infrared heating lamp
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