Cerebral Cortex; Decision Making; Depression; Electrophysiology; Memory; Neurobiology; Neurophysiology; Psychiatry; Schizophrenia; Microscopy, Fluorescence, Multiphoton; Executive Function; Optogenetics
Public Health Interests
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 difficult questions relies on processing different types of information, such as sensory cues, past experience, context, and motivational state. When the information or 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.
- Pinto, L., M.J. Goard, D. Estandian, M. Xu, A.C. Kwan, S.H. Lee, T.C. Harrison, G. Feng, Y. Dan (2013) Fast modulation of visual perception by basal forebrain cholinergic neurons. Nature Neuroscience 16:1857-63.
- Kwan, A.C., and Y. Dan. (2012) Dissection of cortical microcircuits by single-neuron stimulation in vivo. Current Biology 22:1459-1467.
- Lee, S.H., A.C. Kwan, S. Zhang, V. Phoumthipphavong, J.G. Flannery, S.C. Masmanidis, H. Taniguchi, Z.J. Huang, F. Zhang, E.S. Boyden, K. Deisseroth, and Y. Dan. (2012) Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature. 488(7411):379-83.
- Kwan, A.C., S.B. Dietz, G. Zhong, R.M. Harris-Warrick, and W.W. Webb. (2010) Spatiotemporal dynamics of rhythmic spinal interneurons measured using two-photon calcium imaging and coherence analysis. Journal of Neurophysiology 104:3323-3333.
- Kwan, A.C., S.B. Dietz, W.W. Webb, and R.M. Harris-Warrick. (2009) Activity of Hb9 interneurons during fictive locomotion in mouse spinal cord. Journal of Neuroscience 29:11601-11613.
- Kwan, A.C., K. Duff, G.K. Gouras, and W.W. Webb. (2009) Multiphoton-excited intrinsic fluorescence and second harmonic generation in Alzheimer’s disease mouse models. Optics Express 17:3679-3689.
- Kwan, A.C., D.A. Dombeck, and W.W. Webb. (2008) Polarized microtubule arrays in apical dendrites and axons. Proceedings of the National Academy of Sciences 105:11370:11375.