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.
Recent studies in the lab have focused on the secondary motor cortex (M2). As part of the rodent medial prefrontal cortex, M2 is a critical node in the neural circuitry for the flexible control of voluntary 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 neurons with cell-type and pathway specificity. We train head-fixed mice to perform tasks requiring adaptive adjustments of action strategy. 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.
Secondary motor cortex: where 'sensory' meets 'motor' in the rodent frontal cortex
Barthas F, and Kwan AC. Secondary motor cortex: where 'sensory' meets 'motor' in the rodent frontal cortex. Trends in Neurosciences, 40, 181-193 (2017).
Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior.
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).
Longitudinal effects of ketamine on dendritic architecture in vivo in the mouse medial frontal cortex.
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).
Full List of PubMed Publications
- Hill RA, Damisah EC, Chen F, Kwan AC, Grutzendler J: Targeted two-photon chemical apoptotic ablation of defined cell types in vivo. Nat Commun. 2017 Jun 16; 2017 Jun 16. PMID: 28621306
- Barthas F, Kwan AC: Secondary Motor Cortex: Where 'Sensory' Meets 'Motor' in the Rodent Frontal Cortex. Trends Neurosci. 2017 Mar; 2016 Dec 22. PMID: 28012708
- Siniscalchi MJ, Phoumthipphavong V, Ali F, Lozano M, Kwan AC: Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior. Nat Neurosci. 2016 Sep; 2016 Jul 11. PMID: 27399844
- Phoumthipphavong V, Barthas F, Hassett S, Kwan AC: Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex. eNeuro. 2016 Mar-Apr; 2016 Apr 4. PMID: 27066532
- Lee SH, Kwan AC, Dan Y: Interneuron subtypes and orientation tuning. Nature. 2014 Apr 3. PMID: 24695313
- Pinto L, Goard MJ, Estandian D, Xu M, Kwan AC, Lee SH, Harrison TC, Feng G, Dan Y: Fast modulation of visual perception by basal forebrain cholinergic neurons. Nat Neurosci. 2013 Dec; 2013 Oct 27. PMID: 24162654
- Kwan AC, Dan Y: Dissection of cortical microcircuits by single-neuron stimulation in vivo. Curr Biol. 2012 Aug 21; 2012 Jun 28. PMID: 22748320
- Lee SH, Kwan AC, Zhang S, Phoumthipphavong V, Flannery JG, Masmanidis SC, Taniguchi H, Huang ZJ, Zhang F, Boyden ES, Deisseroth K, Dan Y: Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature. 2012 Aug 16. PMID: 22878719
- Yuen D, Wu X, Kwan AC, Ledue J, Zhang H, Ecoiffier T, Pytowski B, Chen L: Live imaging of newly formed lymphatic vessels in the cornea. Cell Res. 2011 Dec; 2011 Nov 15. PMID: 22083511
- Kadiri LR, Kwan AC, Webb WW, Harris-Warrick RM: Dopamine-induced oscillations of the pyloric pacemaker neuron rely on release of calcium from intracellular stores. J Neurophysiol. 2011 Sep; 2011 Jun 15. PMID: 21676929
- Kwan AC, Dietz SB, Zhong G, Harris-Warrick RM, Webb WW: Spatiotemporal dynamics of rhythmic spinal interneurons measured with two-photon calcium imaging and coherence analysis. J Neurophysiol. 2010 Dec; 2010 Sep 22. PMID: 20861442
- Kwan AC: Toward reconstructing spike trains from large-scale calcium imaging data. HFSP J. 2010 Feb; 2010 Jan 22. PMID: 20676302
- Zhong G, Droho S, Crone SA, Dietz S, Kwan AC, Webb WW, Sharma K, Harris-Warrick RM: Electrophysiological characterization of V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J Neurosci. 2010 Jan 6. PMID: 20053899
- Kwan AC, Dietz SB, Webb WW, Harris-Warrick RM: Activity of Hb9 interneurons during fictive locomotion in mouse spinal cord. J Neurosci. 2009 Sep 16. PMID: 19759307
- Kwan AC, Duff K, Gouras GK, Webb WW: Optical visualization of Alzheimer's pathology via multiphoton-excited intrinsic fluorescence and second harmonic generation. Opt Express. 2009 Mar 2. PMID: 19259208
- Kwan AC: What can population calcium imaging tell us about neural circuits? J Neurophysiol. 2008 Dec; 2008 Oct 1. PMID: 18829844
- Kwan AC, Dombeck DA, Webb WW: Polarized microtubule arrays in apical dendrites and axons. Proc Natl Acad Sci U S A. 2008 Aug 12; 2008 Aug 5. PMID: 18682556