Regulation of excitatory-inhibitory balance during motor behavior by neurogliaform interneurons
Alishan Amirali, Department of Neuroscience
Mentor: Aaron Kerlin, Ph.D., Department of Neuroscience
Alishan's research focuses on how a class of inhibitory neurons called NDNF interneurons regulate the balance of excitation and inhibition in the motor cortex during movement. In Parkinson's disease, the loss of dopamine destabilizes motor cortex activity, producing the disorganized firing patterns that underlie symptoms like tremor and bradykinesia. While deep brain stimulation of the subthalamic nucleus is an effective treatment, it can cause unwanted side effects like restlessness by indiscriminately suppressing subcortical motor circuits. NDNF interneurons are a promising alternative target because they naturally enhance the signal-to-noise ratio of motor commands through a dual-action mechanism by simultaneously suppressing noisy dendritic input to pyramidal neurons while disinhibiting their cell bodies. Using two-photon calcium imaging and optogenetic manipulation in mice performing a delayed licking task, Alishan aims to characterize how NDNF neuron activity aligns with motor planning and action initiation, and to establish the causal role of NDNF-mediated dendritic gating in controlling movement. This work lays the mechanistic foundation for identifying precise neuromodulation targets that can restore cortical stability in Parkinson's disease without the limitations of current approaches.
The Effects of Optogenetic Modulation in the Cerebellum during Morphine Conditioned Place Preference
Crystal Clark, Department of Neuroscience
Mentor: Marija Cvetanovic, Ph.D. & Paul Mermelstein, Ph.D., Department of Neuroscience
Research into opioid use disorder often focuses on brain regions traditionally associated with reward processing such as the ventral tegmental area (VTA), a midbrain area critically involved in dopamine signaling. Recent studies, however, have indicated the cerebellum likely plays a role in reward processing, with evidence of involvement in opioid use disorder. Deep cerebellar nuclei (DCN) are the main output from the cerebellum and send glutamatergic projections to the VTA. While stimulation of this circuit has been shown to drive reinforcement behavior, it is not clear how DCN-VTA communication influences opioid seeking behavior. Crystal aims to determine how DCN-VTA activity influences development of morphine conditioned place preference using optogenetic neuromodulation during drug conditioning to inhibit DCN-VTA activity in mice. This work will contribute to understanding how cerebellar activity influences midbrain reward processing and further explore the cerebellum as a potential target for therapeutic interventions.
Advancing Cortical Stimulation as a Treatment Option for Parkinson’s Disease
Noah Hjelle, Department of Neurology
Mentor: Luke Johnson, Ph.D., Department of Neurology
Noah’s project aims to improve treatment for freezing of movement in Parkinson’s disease (PD). His study seeks to understand network changes and therapeutic effectiveness of subdural cortical stimulation of motor and prefrontal cortices. Additionally, he will investigate biomarkers of freezing using machine learning techniques on multi-site simultaneous recordings of the basal ganglia. The outcomes of this project will provide crucial information about the mechanisms underlying freezing of movement and in the long term may lead to improved neuromodulation therapies for PD patients.
Neuromodulation for Seizure Risk Assessment
Brandon Hoang, Department of Neuroscience
Mentor: Esther Krook-Magnuson, Ph.D., Department of Neuroscience & Tay Netoff, Ph.D., Department of Biomedical Engineering
Brandon's research focuses on developing active neural probing methods to estimate seizure risk in real time, leveraging dynamical systems theory to characterize how brain networks transition toward seizures. Epilepsy affects roughly 50 million people worldwide, and approximately one-third remain refractory to existing therapies, in part because seizures appear to occur without warning. While passive monitoring has yielded some informative features, the brain's nonlinear dynamics suggest that actively perturbing the system may reveal latent markers of pre-ictal risk that passive recording cannot. In this project, Brandon develops chronic evoked-response pipelines in rodent models of temporal lobe epilepsy to identify perturbation-based pre-ictal biomarkers and characterize how the network evolves in the lead-up to seizures. He further aims to link evoked-response features to the underlying state for continuous seizure risk estimation. Together, these studies could improve risk assessment, accelerate therapeutic evaluation, and lay groundwork for intervention timed to periods of elevated risk, a step toward adaptive therapies for drug-resistant epilepsy.
Regulating explore-exploit balance through optogenetic modulation of functionally distinct dopamine circuits
Micaela Porod, Department of Neuroscience
Mentor: Nicola Grissom, Ph.D., Department of Psychology and Benjamin Saunders, Ph.D., Department of Neuroscience
Micaela's research focuses on how dopamine acts across distributed striatal circuits to regulate the balance between exploration and exploitation, a core component of adaptive decision making that is often dysregulated in mental health conditions. Striatal dopamine signaling regulates cognitive processes that are central for regulating explore-exploit balance, and dopaminergic dysfunction commonly underlies neuropsychiatric illness. While dopamine circuits represent a major therapeutic target, variability in treatment response highlights critical gaps in our mechanistic understanding of how dopamine shapes adaptive decision making. Dopamine is known to exhibit spatial, temporal, and functional heterogeneity across striatal subregions, suggesting that distinct striatal circuits may differentially mediate explore-exploit behavior. In this project, Micaela aims to parse the contributions of dopamine signaling in the nucleus accumbens and dorsomedial striatum using optogenetic manipulations in mice during a dynamic decision making task. Additionally, she will integrate advanced computational approaches to determine how individual differences in decision making strategies influence sensitivity to neuromodulation. Together, these studies will define how distinct striatal dopamine circuits regulate explore-exploit balance and identify individual factors that mediate responsiveness to circuit perturbation, providing a mechanistic basis for the development of targeted, more effective treatments to improve overall mental health outcomes.
Probing cerebellar contributions to balance adaptation in older adults using transcranial magnetic stimulation
Si-Yu Tsai, Family Medicine and Community Health
Mentor: Jacqueline Palmer, Ph.D., Family Medicine and Community Health
Owing to its distinctive cytoarchitecture and dense neuroanatomical projections to the cerebral cortex, the aging cerebellum may have the potential to counteract age-related decline in the cerebral cortex and preserve behavioral function. Si-Yu Tsai's research aims to investigate the adaptive mechanisms in the cerebellum that enables older adults to rapidly adapt and learn their balance control. Using a multimodal approach that combines neuroimaging and neuromodulation techniques (e.g., dual-site transcranial magnetic stimulation (TMS), TMS-electroencephalography (TMS-EEG), and intermittent theta burst stimulation), this project examines the role of cerebello-cortical functional connectivity in balance adaptation with aging. This work will provide novel insights into the adaptive brain mechanisms that may enable older adults to maintain balance during the advanced stages of aging, with the goal of preserving mobility and extending functional health span.
