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

TY - JOUR

T1 - Thalamic Drive of Cortical Parvalbumin-Positive Interneurons during Down States in Anesthetized Mice

AU - Zucca, Stefano

AU - Pasquale, Valentina

AU - Lagomarsino de Leon Roig, Pedro

AU - Panzeri, Stefano

AU - Fellin, Tommaso

N1 - Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2019/5/6

Y1 - 2019/5/6

N2 - 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.

AB - 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.

KW - Animals

KW - Female

KW - Interneurons/physiology

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Parvalbumins/metabolism

KW - Somatosensory Cortex/physiology

KW - Thalamus/physiology

U2 - 10.1016/j.cub.2019.04.007

DO - 10.1016/j.cub.2019.04.007

M3 - SCORING: Journal article

C2 - 31031117

VL - 29

SP - 1481-1490.e6

JO - CURR BIOL

JF - CURR BIOL

SN - 0960-9822

IS - 9

ER -