To understand how the brain works, it is crucial to identify the causality of the neural circuits that lead information flow through the whole brain network during certain behavior or task. We develop strategies to visualize and modulate the activity of specific cell populations across the brain using genetically encodable imaging tools. Especially we focus on developing the hemogenetic fMRI technique from multiple engineering standpoints, including engineering MRI reporter genes, advancing MRI acquisition sequences and computational models for functional connectivity analysis.

Dopamine is an important neuromodulator for reward, learning and memory. The functional dopamine-related circuitry from the midbrain to striatum remains elusive. By integrating multi-model imaging, recording, and modulation techniques, we aim to study presynaptic inputs of midbrain dopaminergic neurons, dopamine release, dopamine receptor occupancy and postsynaptic consequences of striatal medium spiny neurons, and explore the malfunctioned circuitry and molecular markers in brain disorders, such as depression, addiction, OCD, Parkinson's Disease, etc.

Astrocytes, about 19 - 40% of brain cells, play critical roles in brain metabolism, immune functions, and neural modulation. In the striatum, the interaction between astrocyte and medium spiny neurons was found to regulate the plasticity of the nucleus accumbens. More importantly, astrocyte dysfunction has been found in several mental disorder diseases, including OCD and Huntington Disease. Analysis of the spatiotemporal characteristics of astrocytes and neurons in vivo will provide insights into the roles of astrocytes in healthy and diseased brains, which could potentially facilitate clinical applications.

The adult human brain contains more than 400 miles of vasculature, delivering oxygen and nutrients to billions of cells in the brain. In the adult rat's neocortex, the mean distance of the center of neuronal somata to the closest microvessel is reported to be around 15 μm. The blood flow is finely targeted to active brain areas through delicately controlled vasodilation and contraction. This hemodynamic response is the basis of blood-oxygenation-level-dependent (BOLD) fMRI, which is the dominant neuroimaging technique used in human brain cognitive studies and clinical applications. A better understanding of the fundamental mechanism of the neurovascular coupling unit (NVC) will facility interpretation of human fMRI results and improve experimental design for cerebral vascular disease-related brain function studies.