Alex Kwan, PhD
Research & Publications
Biography
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Research Summary
We are broadly interested in the function of the medial frontal cortex. Many of our experiments involve cellular-resolution optical imaging and head-fixed mouse behavior. We have made progress in two specific areas:
Psychiatric drugs
Numerous chemical compounds have the ability to alter our perception, cognition, and mood. The behavioral effects are often long-lasting, presumably because drugs can act on synapses and dendrites to induce plasticity in the brain. However, to date, most of our knowledge of drug action on dendrites have come from studies of neuronal cultures and brain slices. In the lab, we are measuring the impact of psychoactive drugs on cortical microcircuits and dendritic signaling in awake, behaving mice. Insights gained from our studies may facilitate the development of new medicines for mental illnesses. Current projects focus on compounds with fast-acting antidepressant effects (ketamine), serotonergic psychedelics (psilocybin), and their potential interactions with risk genes (Shank3, Scn2a).
Flexible decision-making
In a dynamic environment, animals must adjust their action plans to match the behavioral demands. For example, the same sensory stimulus may require different motor responses depending on the context. The mammalian prefrontal cortex is thought to be a central node mediating flexible behavior, however the synaptic and circuit mechanisms remain poorly understood. In the lab, we are adapting classic decision-making tasks for head-fixed mice. These tasks involve switching sensory-response contingencies or uncertain response-outcome relations. We perform optical imaging and perturbation experiments to study the task-related neural dynamics. We use computational models to dissect the choice behavior, for example by fitting reinforcement learning algorithms. Recent studies in the lab have focused on the role of the mouse secondary motor cortex (M2 / MOs) and cingulate cortex (Cg1 / ACAd), medial frontal regions that are involved in binding prior events to current decisions.
Coauthors
Research Interests
Antidepressive Agents; Decision Making; Dendrites; Depressive Disorder; Electrophysiology; Microscopy, Fluorescence; Prefrontal Cortex; Optogenetics
Selected Publications
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo.Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, Kwan AC. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron 2021, 109: 2535-2544.e4. PMID: 34228959, PMCID: PMC8376772, DOI: 10.1016/j.neuron.2021.06.008.
- A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics.Savalia NK, Shao LX, Kwan AC. A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics. Trends In Neurosciences 2021, 44: 260-275. PMID: 33358035, PMCID: PMC7990695, DOI: 10.1016/j.tins.2020.11.008.
- Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines.Ali F, Gerhard DM, Sweasy K, Pothula S, Pittenger C, Duman RS, Kwan AC. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Nature Communications 2020, 11: 72. PMID: 31911591, PMCID: PMC6946708, DOI: 10.1038/s41467-019-13809-8.
- Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity.Barthas F, Hu MY, Siniscalchi MJ, Ali F, Mineur YS, Picciotto MR, Kwan AC. Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity. Biological Psychiatry 2020, 88: 541-553. PMID: 32276717, PMCID: PMC7434704, DOI: 10.1016/j.biopsych.2020.02.008.
- Interpreting in vivo calcium signals from neuronal cell bodies, axons, and dendrites: a review.Ali F, Kwan AC. Interpreting in vivo calcium signals from neuronal cell bodies, axons, and dendrites: a review. Neurophotonics 2020, 7: 011402. PMID: 31372367, PMCID: PMC6664352, DOI: 10.1117/1.NPh.7.1.011402.