Department of Neuroscience
Mentor: Aaron Kerlin, Ph.D., Department of Neuroscience
Project: Regulation of excitatory-inhibitory balance during motor behavior by neurogliaform interneurons
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.
