Establish Which Brain Regions Constitute the Physical Substrate of Consciousness in the Brain: Identification of Cortical and Thalamic Areas/Cell Types That Constitute the Full NCC
INSTITUTE: University of Wisconsin-Madison / Department of Psychiatry / Center for Sleep and Consciousness
PROJECT LEADER: Chiara Cirelli
PROJECT DURATION: 3 years
LAB WEBSITE: Center for Sleep and Consciousness
We still know very little about the critical changes in neural activity that occur in the cerebral cortex and thalamus around the time consciousness is lost (LOC) or recovered (ROC). One reason is that only a few cortical or thalamic areas have been studied in previous experiments, and only one at a time. Our goal is to gain a more comprehensive view of what changes at LOC and ROC by using novel high-density electrodes that can record from thousands of neurons simultaneously and span a large part of the mouse brain. LOC/ROC will be characterized across the sleep/wake cycle, under anesthesia, and in a pharmacologically induced coma-like state. By taking advantage of the genetic tools that are available in mice, we will also activate or inhibit specific neuronal populations and test their effects on LOC and ROC. LOC/ROC will be determined behaviorally, using the loss of righting reflex and a standardized battery of behavioral tests for consciousness that we have developed for rodents.
Figure 1. Identifying the critical changes at LOC and ROC using high density Neuropixels electrodes in mice. The figure shows the activity of neurons in cortex, hippocampus, and thalamus (top to bottom) during 20-sec of waking (left), NREM sleep (middle), and REM sleep (right). Each line represents a neuron, and each dot is one spike of that neuron.
By combining high-density recordings with the stimulation of specific neuronal groups, we will also test whether the Perturbational Complexity Index – PCI – works in rodents. In humans, PCI is an established tool used to infer levels of consciousness based the complexity of the cortical response triggered by transcranial magnetic stimulation (TMS)(Casali et al., 2013; Casarotto et al., 2016). When consciousness is present, for example during waking and REM sleep, TMS stimulation triggers complex responses that lead to high PCI values. By contrast, stereotyped responses during dreamless NREM sleep, deep anesthesia, or coma, lead to low values of PCI. In rodents we will test an adaptation of PCI (PCIst) obtained by electrically and/or optogenetically stimulating different cortical areas, and see whether it can distinguishes among conscious and unconscious states just as it does in humans. If successful, these studies will supplement the behavioral assessment of LOC/ROC with the direct assessment of the level of consciousness through a PCI-like index, as can be done in unresponsive humans.
Broader Impact:
This project will allow us to better understand whether the full neural correlate of consciousness (NCC) is constituted by neurons in specific cortical areas, cortical layers, or cortical cell types, and will elucidate the role of the thalamus and thalamic cells in the full NCC. By testing a PCI measure in rodents, it will also answer the question of whether loss and recovery of consciousness in animal models is associated with a breakdown of information integration.
Publication:
Mayner, William GP, et al. "Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex." Eneuro (2022).