Cellular diversity

Phasic changes in neuronal activity of the external globus pallidus (GPe) are observed with movements. In contrast, the activity of GPe neurons precipitates into synchronous rhythmic bursting in animal models and patients of Parkinson’s disease (PD). Despite the imminent behavioral and disease relevance of the GPe, its cellular makeup and heterogeneity have not been fully appreciated nor investigated. In the past few years, our laboratory has addressed this knowledge gap by identifying two principal GPe neuron classes, which can be distinguished by their non-overlapping expression of the molecular markers parvalbumin and Npas1. Furthermore, our group has demonstrated that parvalbumin neurons and Npas1 neurons have distinct cellular and circuit properties; yet, compelling data from our group and others suggest the existence of an additional principal class that accounts for up to 15–20% of the total GPe neuron population. By utilizing a multidisciplinary approach, our goal is to define this neuron class in the GPe by its birthplace, lineage identity, genetic profile, electrophysiological signature, axonal projection, excitatory inputs, and behavioral relevance. Our research challenges the prevailing circuit model and will add to the knowledge of the long-understudied GPe and its alterations with PD. The successful achievement of these aims will define the role of the GPe in behavioral and disease contexts.

Inter-cell communications

An effective communication in the brain involves proper controls of how signals are generated, how they are terminated, and how they are spatiotemporally distributed. This process involves a complex architecture of ion channels, receptors, synapse, release and clearance machinery, etc. Our lab studies how this is achieved and how it is altered in disease conditions. The main focus is on intrinsic excitability, neurotransmission, and their regulation by astrocytes.

Other ongoing research

Stress-anxiety driven motor behavior, astrocyte physiology, dystonia, and Alzheimer’s disease.

Neurodegenerative diseases

To date, millions of people in the US suffer from neurodegenerative diseases. Current therapeutic strategies are limited, short-lived, and ineffective. Our research seeks to provide the mechanisms that underlie the pathogenesis of Alzheimer's Disease, Parkinson’s disease, and Huntington’s Disease. We hope to translate our insights into developing novel treatments for these neurological disorders.

Alzheimer's disease is the most common neurodegenerative disease and it is the most common underlying cause of dementia. It affects primarily the cortex and hippocampus. Severe synapse loss and inclusions can be observed. Our research seek to delineate the cellular processes that lead to the network dysfunction and the endogenous clearing mechanism of oligomers.

Parkinson’s disease and Huntington’s disease are the two major neurodegenerative diseases that affect the motor function. Our research interests center on better understanding the cellular and molecular building blocks that make up the basal ganglia macrocircuit as well as their implications in both health and disease.