Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons
Rong Mao,
Matias Lorenzo Cavelli,
Graham Findlay,
Kort Driessen,
Michael J. Peterson,
William Marshall,
Giulio Tononi,
Chiara Cirelli
Affiliations
Rong Mao
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53719, USA
Matias Lorenzo Cavelli
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Departamento de Fisiología de Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay
Graham Findlay
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53719, USA
Kort Driessen
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53719, USA
Michael J. Peterson
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA
William Marshall
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Department of Mathematics and Statistics, Brock University, St. Catharines, ON L2S 3A1, Canada
Giulio Tononi
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Corresponding author
Chiara Cirelli
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Corresponding author
Summary: The cerebral cortex is widely considered part of the neural substrate of consciousness, but direct causal evidence is missing. Here, we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.
