Adrenergic signaling can both induce a hypnotic state (through the alpha-2a receptor) or alternatively can speed emergence (as seen with locus coeruleus stimulation.) We are interested in the circuits involved in both of these processes and using a combination of genetic and opto/chemogenetic tools to map the relevant circuits.
By studying behavioral dynamics at unchanging pharmacologic concentrations, our lab has developed a sensitive toolset for distinguishing individuals' hypnotic sensitivity and a novel measure related to behavioral dynamics, their state stability. We are investigating the effect of specific neural populations on these precise measures, hypothesizing that activity of neural populations affecting these measures are a significant contributor to interindividual differences seen in anesthetic response.
Similar to shifts between discrete activity patterns during sleep, the brain spontaneous shifts among discrete neurophysiologic patterns of activity during general anesthesia even in the absence of stimulus and steady drug concentration. These states have functional significance, as emergence from anesthesia only occurs from a subset. We are investigating additional functional significance of these states by testing state-related stimulus responses. We are additionally interested in neural mechanisms of state stability and change, and are using chemogenetic methods to explore circuit specific contributions to global EEG-based state change.
Electrographic Evidence for Individual Neural Inertia in Mice that Decreases with Time. Frontiers in Systems Neuroscience (2022)
Recovery of consciousness and cognition after general anesthesia in humans Elife. (2021)
Resistance to state transitions in responsiveness is differentially modulated by different volatile anaesthetics in male mice. British Journal of Anaesthesia. (2020)
Resistance to state transitions in responsiveness is differentially modulated by different volatile anaesthetics in male mice. Elife. (2019)
Azi-medetomidine: Synthesis and Characterization of a Novel α2 Adrenergic Photoaffinity Ligand. ACS Chemical Neuroscience. (2019)
Optoanesthesia: Use of Anesthetic Photolabels In Vivo. Methods in Enzymology. (2018)