Our goal is to achieve a mechanistic understanding of fundamental cognitive processes whose dysfunctions are implicated in neuropsychiatric disorders. Currently we are focusing on memory generalization—the cognitive process of extending what we have learned from past experience to new situations, which is essential for us to adapt to the ever-changing environment. To elucidate the neuronal mechanisms underlying generalization, we are delineating the underlying brain circuits and exploring the neuronal principles these circuits operate on.
Both lack of and over- generalization of memories lead to brain malfunctions. For example, lack of generalization accounts for the behavioral inflexibility in autism spectrum disorders, while over-generalization of fear memories underlies post-traumatic stress disorder (PTSD) and anxiety. Interestingly, clinical studies found that patients of schizophrenia have selective impairment in memory generalization but no alterations in global memory functions. We are working to determine the roles of the neuronal circuits regulating memory generalization in the pathogenesis of psychosis. We aim to identify precise targets for novel antipsychotic therapy with minimal side effects and this will benefit many patients affected by the side effects of currently available medications.
We integrate state-of-art techniques to explore brain circuits at multiple levels. Our major approaches include real-time observations of neuronal activities in behaving animals, electrophysiological characterization of neuronal interactions in the circuits, and selective targeting and manipulation of specific neuronal and synaptic properties in the brain. In addition to applying existing methods, we also invest in developing novel technology to facilitate our discovery. We are particularly interested in making new tools to elucidate the wiring and rewiring of long-range poly-synaptic circuits and use them to reveal circuitry mechanisms underlying memory generalization and psychosis.