RESUMO
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.
RESUMO
In humans, the level of consciousness is assessed by quantifying the spatiotemporal complexity of cortical responses using Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). Here we validate PCIst in freely moving rats and mice by showing that it is lower in NREM sleep and slow wave anesthesia than in wake or REM sleep, as in humans. We then show that (1) low PCIst is associated with the occurrence of an OFF period of neuronal silence; (2) stimulation of deep, but not superficial, cortical layers leads to reliable PCIst changes across sleep/wake and anesthesia; (3) consistent PCIst changes are independent of which single area is being stimulated or recorded, except for recordings in mouse prefrontal cortex. These experiments show that PCIst can reliably measure vigilance states in unresponsive animals and support the hypothesis that it is low when an OFF period disrupts causal interactions in cortical networks.
RESUMO
Cognitive processes are carried out during wakefulness by means of extensive interactions between cortical and subcortical areas. In psychiatric conditions, such as psychosis, these processes are altered. Interestingly, REM sleep where most dreams occurs, shares electrophysiological, pharmacological, and neurochemical features with psychosis. Because of this fact, REM sleep is considered a natural model of psychosis. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that at sub-anesthetic dose induces psychotomimetic-like effects in humans and animals, and is employed as a pharmacological model of psychosis. Oscillations in the gamma frequency band of the electroencephalogram (EEG), mainly at about 40 Hz, have been involved in cognitive functions. Hence, the present study was conducted to analyze the EEG low gamma (30-45 Hz) band power and coherence of the cat, in natural (REM sleep) and pharmacological (sub-anesthetic doses of ketamine) models of psychosis. These results were compared with the gamma activity during alert (AW) and quiet wakefulness (QW), as well as during non-REM (NREM) sleep. Five cats were chronically prepared for polysomnographic recordings, with electrodes in different cortical areas. Basal recordings were obtained and ketamine (5, 10, and 15 mg/kg, i.m.) was administrated. Gamma activity (power and coherence) was analyzed in the abovementioned conditions. Compared to wakefulness and NREM sleep, following ketamine administration gamma coherence decreased among all cortical regions studied; the same coherence profile was observed during REM sleep. On the contrary, gamma power was relatively high under ketamine, and similar to QW and REM sleep. We conclude that functional interactions between cortical areas in the gamma frequency band decrease in both experimental models of psychosis. This uncoupling of gamma frequency activity may be involved in the cognitive features shared by dreaming and psychosis.
