Alex Kwan, PhD

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

Psychoactive drugs

Numerous chemical compounds have the ability to alter our perception, cognition, and mood. The behavioral effects are often long-lasting, presumably because some of the drugs can act on synapses and dendrites to induce plasticity in neural circuits. However, to date, most of our knowledge of drug action on dendrites have come from studies of neuronal cultures and brain slices. In behaving animals, dendritic excitability is strongly influenced by background activity, neuromodulation, and inhibitory inputs. In the lab, we are using systems neuroscience approaches to measure the impact of psychoactive drugs on cortical microcircuits and dendritic signaling in mice in vivo. Current projects focus on compounds with antidepressant effects (ketamine, psilocybin), and their potential interactions with risk genes (Shank3, Scn2a).

Flexible decision-making

In a dynamic environment, animals must adjust their action plans to match the behavioral demands. For example, the same sensory stimulus may require 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 adapting classic decision-making tasks for head-fixed mice. These tasks involve switching sensory-response contingencies or uncertain response-outcome relations. We perform optical imaging and perturbation experiments to study the task-related neural dynamics. We use computational models to dissect the choice behavior, for example by fitting reinforcement learning algorithms. Recent studies in the lab have focused on the role of the mouse secondary motor cortex (M2 / MOs) and cingulate cortex (Cg1 / ACAd), medial frontal regions that are involved in binding prior events to current decisions.