The Neural Basis of Anesthesia
Principal Investigator: Dr. Aeyal Raz
Although general anesthetics have been in widespread use for more than 150 years, how they produce loss of consciousness (LOC) remains one of the great unsolved mysteries in biomedical science. Research on anesthetic mechanisms and the neural correlates of consciousness have converged over the past few years, suggesting a number of intriguing models such as information integration and predictive coding. Anesthetics can reliably induce a reversible, controlled LOC, enabling the ongoing research into these mechanisms. However, many of the current models are based on non-invasive studies using EEG and functional MRI techniques with limited spatial and temporal resolution. However, since these methods do not directly measure neuronal spiking and synaptic activity, the effects of anesthetics on local network activity cannot be determined.
Recently, we showed a preferential effect of volatile anesthetic on ascending pathways in the sensory (auditory) system. This finding is consistent with some of the new models of sensory awareness in which information from the outside world carried by bottom-up pathways is integrated with top-down information about context and expectation to form a sensory percept. LOC occurs when interconnectivity of separate modules or feedback pathways carrying predictive signals are disrupted, even with intact ascending sensory input.
In the Neural Basis of Anesthesia Laboratory, headed by Dr. Aeyal Raz, we use electrophysiology and optogenetics methods to assess the effects of anesthetics on specific pathways in the brain, and the molecular and cellular mechanisms responsible for these effects. The studies are conducted in isolated brain slices that enable clean investigation into the anesthetic influence of multiple anesthetics targeting different molecular loci to identify the final common neural network pathways that lead to LOC.