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
The goal of my laboratory is to understand the neural circuit basis of high-level cognitive functions, which are essential for goal-directed behavior and commonly impaired in psychiatric disorders. Using the mouse as a model enables us to apply a diverse set of tools, including in vivo two-photon imaging, optogenetics, and patch-clamp electrophysiology, to relate neural activity to behavior. We are particularly interested in the prefrontal and cingulate cortices that are central nodes of the cognitive circuits.
Specialized Terms: Neural circuits; Inhibitory neurons; Executive functions; Working memory; Decision-making; Action selection; Two-photon microscopy; Optogenetics; Mouse behavior; Electrophysiology
Extensive Research Description
My laboratory is engaged in two major problems. One, can we break down cognitive behaviors into component processes and determine how they are implemented in the brain? We have trained head-fixed mice to perform a variety of operant tasks involving perceptual decision-making, timing, and short-term memory. In behaving mice, we use optical methods to image and control neuronal ensemble activity. We are exploiting these paradigms to study the roles of cell types, neural pathways, and neuromodulation in cognitive behaviors. Two, how do mental illnesses and psychiatric drugs impact neural activity? We want to bring our expertise in cellular resolution optical imaging to study the actions of antipsychotic and antidepressant drugs on cortical microcircuits. We are working with other basic and clinical research groups on this topic.
- 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.