Decision Making; Depressive Disorder; Electrophysiology; Microscopy, Fluorescence; Schizophrenia; Prefrontal Cortex; Executive Function
Public Health Interests
Alzheimer's Disease; Depression; Schizophrenia
Swartz Program in Theoretical Neurobiology
We want to understand the neural circuits that enable flexibility in choice behavior.
Every day we make hundreds of decisions. Should I choose an original glazed or a honey cruller? Should I even eat a donut? Answering such questions relies on processing different types of information, such as sensory cues, past experience, context, and motivational state. When contingencies change, we adapt. The capacity to be flexible in choice behavior is a remarkable and essential part of our cognitive life. By contrast, cognitive rigidity is a core symptom in neuropsychiatric disorders.
There is extensive evidence linking prefrontal and higher-order motor cortical regions to flexible behavior. These regions exert executive control to guide actions. Still unknown, however, are how internal and external information are processed for action control, how choices are represented by neuronal ensembles, and how signals are routed to other brain regions to influence motor output.
We design experiments to answer these questions in mice, leveraging genetic and molecular approaches to identify the cell-type and pathway-specific components of the brain circuits. We train mice to perform tasks requiring adaptive, goal-directed actions. We use a combination of techniques to characterize and manipulate neural activity, including two-photon calcium imaging, optogenetics, and computational modeling.
A related research interest of the lab is to apply these behavioral and neurophysiological methods to the study of mouse models of neuropsychiatric disorders. We are particularly interested in the longitudinal effects of chronic stress and antidepressants on the frontal cortical circuitry.
- Barthas F, and Kwan AC. Secondary motor cortex: where 'sensory' meets 'motor' in the rodent frontal cortex. Trends in Neurosciences, in press.
- Siniscalchi MJ, Phoumthipphavong V, Ali F, Lozano M, and Kwan AC. Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior. Nature Neuroscience, 19, 1234-1242 (2016).
- Phoumthipphavong V, Barthas F, Hassett S, and Kwan AC. Longitudinal effects of ketamine on dendritic architecture in vivo in the mouse medial frontal cortex. eNeuro, 3(2):0133-15.2016 (2016).