Driessen, K. | Search bioRxiv

bioRxiv2024

Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons

The cerebral cortex is widely considered part of the neural substrate of consciousness. However, while several studies have demonstrated that stimulation of subcortical nuclei can produce EEG activation and restore consciousness, so far no direct causal evidence has been available for the cortex itself. 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.

neuroscience↗

bioRxiv2022

Sleep/wake changes in perturbational complexity in rats and mice

In humans, the level of consciousness can be assessed by quantifying the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). These measures are consistently high in wake and rapid eye movement (REM) sleep and low in dreamless non-REM (NREM) sleep, deep slow wave anesthesia, and coma. The neuronal mechanisms underlying the reduction of PCI/PCIst in unconscious states remain largely unexplored. The extent to which different cortical areas or layers contribute to these measures is also unknown. To address these questions, here we first validate the use of PCIst in freely moving rats (8 males) and mice (12, 4 females) by showing that its values are lower in NREM sleep and slow wave anesthesia than in wake or REM sleep, as in humans. We then show that low PCIst is associated with the occurrence of an OFF period of neuronal silence. Moreover, the stimulation of deep, but not superficial, cortical layers leads to reliable changes in PCIst across sleep/wake and anesthesia. Finally, consistent changes in PCIst can be measured independent of which single area is being stimulated or recorded, except for recordings in mouse prefrontal cortex. These experiments directly support the hypothesis that PCIst is low when an OFF period disrupts causal interactions in cortical networks. Moreover, they demonstrate that, as in humans, PCIst can be used for the reliable assessment of vigilance states in unresponsive animals, without the need to rely on behavioral outputs such as the righting reflex. Significance StatementThe level of consciousness can be assessed in humans by measuring the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst. These measures discriminate between conscious and unconscious conditions with high sensitivity and specificity and work in unresponsive patients. However, the neuronal mechanisms underlying PCI/ PCIst are largely unexplored. Moreover, since they reflect evoked responses from many cortical regions, it is unclear whether some areas or layers are more informative than others. Here we validate PCIst in rodents, provide direct evidence for the underlying neuronal mechanisms, and show that reliable changes in PCIst can almost always be obtained independent of which single area is stimulated or recorded, but only after stimulation of deep layers.

neuroscience↗