Alex Kwan, PhD
Research & Publications
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:
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).
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.
Antidepressive Agents; Decision Making; Dendrites; Depressive Disorder; Electrophysiology; Microscopy, Fluorescence; Prefrontal Cortex; Optogenetics
- Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and PsilocybinDavoudian P, Shao L, Kwan A. Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin ACS Chemical Neuroscience 2023, 14: 468-480. PMID: 36630309, PMCID: PMC9898239, DOI: 10.1021/acschemneuro.2c00637.
- Psychedelics and Neural Plasticity: Therapeutic Implications.Grieco S, Castrén E, Knudsen G, Kwan A, Olson D, Zuo Y, Holmes T, Xu X. Psychedelics and Neural Plasticity: Therapeutic Implications. Journal Of Neuroscience 2022, 42: 8439-8449. PMID: 36351821, PMCID: PMC9665925, DOI: 10.1523/jneurosci.1121-22.2022.
- The neural basis of psychedelic actionKwan A, Olson D, Preller K, Roth B. The neural basis of psychedelic action Nature Neuroscience 2022, 25: 1407-1419. PMID: 36280799, PMCID: PMC9641582, DOI: 10.1038/s41593-022-01177-4.
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivoShao 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 PsychedelicsSavalia NK, Shao LX, Kwan AC. A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics Trends In Neurosciences 2020, 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 spinesAli 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.