Summary of Current Research

Brain circuits provide substrates for the diverse and dynamic brain functions. We aim to understand how these circuits carry the information flow in the brain for defined functions and how they are changed and modulated by disease, brain state and behavioral context. We employ multidisciplinary approaches including imaging, electrophysiology, modern anatomy, molecular genetics, and computation to examine the principles governing neuronal connectivity and their regulation. In parallel, we push for cutting-edge tool development, improvement and implementation, and computational algorithm development since many of the fundamental questions we ask are limited by the available techniques. A summary of all our current efforts can be found on our projects page.

One example is the ongoing effort to understand the connectivity and modulation of the basal ganglia. The basal ganglia are critical for many fundamental brain functions, such as movement control and decision-making. Dysfunction of the basal ganglia contributes to the pathophysiology of many neurodegenerative diseases, most notably Parkinson's disease and Huntington's disease. Neuroscientists’ understanding of the basal ganglion has been limited by the complexity of the circuitry. For example, increasing evidence suggests that neurons in the basal ganglia are heterogeneous, yet little is known about the anatomical and functional connectivity of individual cell types.

In my laboratory, we examine the functional connectivity within basal ganglia and their interaction with cerebral cortex and thalamus. We target defined cell types by combining novel functional circuit analysis tools and molecular genetic technology with classical anatomical tracing. We also use two-photon imaging with genetically encoded calcium sensors to study the signal transduction events in basal ganglia that underlie the dynamics of functional circuitry.

Alterations in basal ganglia circuits are also associated with behavioral perturbations in drug addiction and neurodegenerative diseases. A mid-term goal of our research program is to investigate how the circuitry changes during different behaviors (e.g. goal-directed vs. habitual), and in animal models of addiction.

These projects are expected to be synergistic. With these complementary approaches, we aim to determine cell-type specific circuitry, a prerequisite for a mechanistic understanding of basal ganglia function in health and disease.