PROJECT SUMMARY/ABSTRACT
General anesthetics are essential in medicine, providing unconsciousness, amnesia and analgesia for
otherwise intolerable surgical procedures. Although general anesthetics are widely used, little is known about
how the brain recovers consciousness after general anesthesia. Consequently, there are no available
treatments for common clinical problems associated with recovery from general anesthesia, such as
emergence delirium and delayed emergence. Recent studies demonstrate that subcortical arousal nuclei are
important for recovery of arousal, but mechanisms underlying recovery of cognition have not been explored.
There are important knowledge gaps that this research program intends to fill over the next five years.
First, the trajectory of cognitive recovery during anesthetic emergence is unknown. Specifically, it is unclear
how discrete cognitive domains recover, and how the recovery trajectory differs among commonly used
anesthetic drugs with different mechanisms of action. Second, it is unknown whether there are sex differences
in cognitive recovery from general anesthesia, and whether different stages of the estrous cycle alter the
cognitive recovery profile in female rodents. Finally, it its unknown if activating neural circuits involved in
arousal, attention, and memory facilitate cognitive recovery from general anesthesia.
The broad, long-term objectives of this R35 (MIRA) grant are to elucidate how cognition
recovers after general anesthesia, and to develop novel approaches to accelerate recovery. First, we
will use touchscreen-based cognitive testing of rats to establish how specific cognitive domains recover after
general anesthesia. Second, we will determine whether the female estrous cycle influences cognitive recovery.
Finally, we will use chemogenetic manipulations to activate neural circuits involved in arousal, attention, and
memory to test for acceleration of cognitive recovery. These studies will inform and guide novel approaches to
accelerate recovery of consciousness after general anesthesia and treat common clinical problems associated
with anesthetic emergence. They will also provide new insights into fundamental mechanisms of
consciousness and cognition.