Memory Processing in Prefrontal Microcircuits
Memory is a critical brain function that is thought to provide meaning to existence particularly because it interacts with and supports so many other vital functional domains, including emotional processing, learning, decision making, creativity and language. Disturbances of memory, therefore, significantly diminish quality of life and also contribute to a number of disorders including Alzheimer’s, fronto-temporal dementias, drug addictions and post-traumatic stress disorder. My lab is therefore interested in unraveling the genetic and circuit level mechanisms by which memories form, stabilize, and reorganize over time. An area particular devoid of mechanistic understanding are the mechanisms the brain uses for top-down goal-directed memory processing, where prior knowledge is used to guide future learning, in a way that can enable (or impede) cognitive flexibility and creativity.
To achieve these goals, the lab uses a multi-disciplinary approach to observe and control neural dynamics spanning multiple brain regions and over chronic timescales in the behaving animal. We develop cognitive behavioral tasks that can be performed by rodents in a head-fixed virtual environment, and use novel surgical preparations, to optically access and record neural activity over large volumes in behaving animals at cellular resolution. These experiments are then coupled with real-time optogenetic stimulation to bias the animal’s neural activity and resulting behavior. We have also developed tools to overlay gene-expression information on top of the acquired functional datasets at cellular resolution in an effort to inform the molecular mechanisms that give rise to the observed circuit dynamics and behavior. We hope that a combined genetic and circuits approach will begin to provide a more comprehensive understanding of top-down goal-directed cognitive processes in the mammalian brain.