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 adaptive 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.
We have evidence indicating that prefrontal and higher-order motor cortical regions mediate flexibility. These regions exert executive, rather than direct, 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 cellular components of cortical circuits. We train mice to perform tasks requiring adaptive, goal-directed actions. We use a combination of techniques to characterize neural ensemble dynamics, including two-photon calcium imaging, optogenetics, and computational modeling.
- 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.
- Activation of specific interneurons improves V1 feature selectivity and visual perception. 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) Nature. 2012 Aug 16;488(7411):379-83. doi: 10.1038/nature11312.
- 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.