Research

We are broadly interested in the structure and function of frontal cortical circuits. Many of our experiments involve cellular-resolution optical imaging and head-fixed mouse behavior. We have made progress in two specific areas:

Flexible decision-making

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In a changing environment, animals must adjust their action plans to match the behavioral demands. For example, the same sensory stimulus can lead to different motor responses depending on the context. The mammalian prefrontal cortex is thought to be a central node mediating flexible behavior, however the synaptic and circuit mechanisms remain poorly understood. In the lab, we are designing tasks with switching sensory-response or response-outcome contingencies for head-fixed mice. We are performing optical imaging, electrophysiological, and perturbation experiments. Recent studies in the lab have focused on the role of the mouse secondary motor cortex (M2).


Chronic stress and antidepressants

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We want to delineate the impact of chronic stress and antidepressants on the frontal cortical circuitry. Because the time course of pathophysiology can vary greatly across individuals, a major goal of our research is to perform longitudinal, within-subject studies. To this end, we are developing cellular-resolution optical imaging methods to capture structural and functional plasticity in vivo.  In a recent study, we characterized effects of a fast-acting antidepressant on dendritic spine turnover. We used longitudinal two-photon imaging to show that a single dose of ketamine leads to a sustained increase in the rate of spine formation in the mouse medial frontal cortex. The basic science findings may lead to better methods to diagnose and treat depression.

Funding

We are grateful for current and past support from NIMH, NIA, Simons Foundation, Brain & Behavior Research Foundation, Inscopix, and Epilepsy Foundation.