[
International Worm Meeting,
2021]
The innovation of anesthesia with volatile anesthetic agents has made modern surgical practice possible. The anesthetized state is defined by behavioral criteria and is today largely monitored through physiological measurements such as hemodynamics and gas exchange. These measurements are sometimes supplemented by EEG derived metrics, but the relationship between these metrics and the neurophysiological mechanisms of anesthesia is entirely unknown. We have used cellular resolution multi-neuronal functional imaging in C. elegans as a powerful model for bridging the gap between single-neuron activity and whole nervous system dynamics under anesthesia. We previously found that the anesthetic state in C. elegans corresponds to a loss of synchrony in global neural dynamics as opposed to generalized depression of individual neuron activity. Here we extend this work by examining how the nervous system of C. elegans recovers from the anesthetic state of dissynchrony to normal function. Employing a light-sheet diSPIM microscope we can measure the activity of the majority of neurons in the C. elegans head as the animal emerges from anesthesia. We observe that correlation in activity between neuron pairs, which is significantly suppressed in the anesthetized state, recovers to near pre-exposure levels in a non-linear, cyclical manner over several hours. Notably, the time required for this recovery is significantly longer then the time needed to induce the neurological anesthetic state. This finding recapitulates the concept of "neural inertia", a proposed hysteresis in the processes of anesthesia induction and emergence well-characterized in humans by the observation that emergence from anesthesia tends to occur at lower concentrations of drug than are required for induction. Because C. elegans perform gas exchange through diffusion, the differences we observe in time needed for induction and emergence are consistent with the phenomenon characteristic of neural inertia in humans. This finding further demonstrates the utility of C. elegans as a model system for investigating the effects of anesthesia on neuronal function and the physiological basis of those effects.