About WeiXing Shi, PhD

Neurobiology & Pharmacology of Monoamine Systems in Brain Disorders

My research investigates the neurobiological basis of schizophrenia, Parkinson’s disease, ADHD, and drug addiction by examining how dopamine (DA) neuron activity interacts with prefrontal cortex (PFC) function. Utilizing techniques including electrophysiology (in vivo/vitro), optogenetics, chemogenetics, and fiber photometry, we dissect the neural circuits underlying these disorders.

Dopamine Neuron Regulation: A central focus is understanding how midbrain DA neurons and their projections (nigrostriatal, mesolimbic, mesocortical) are modulated by intrinsic and extrinsic inputs, including pharmacological agents like amphetamine and L-DOPA. We have discovered that amphetamine and related psychostimulants excite DA neurons via adrenergic α1 receptors – an effect independent of DA receptors. This finding offers a potential explanation for the persistent addictive properties of these drugs, even in DA transporter-knockout models.

Dynamic DA-PFC Interaction: Given the PFC’s critical role in executive function and its involvement in disorders affecting DA systems, we are investigating how it regulates DA neuron activity. Our work demonstrates that psychostimulants increase the duration of “Up states” within the PFC via adrenergic α1 receptors, mirroring their excitatory effect on DA neurons. Furthermore, we have observed correlated activity between DA and PFC neurons at a subsecond timescale, which is dynamically altered by psychostimulant exposure. Current research aims to identify the specific neural pathways mediating this crucial DA-PFC interaction and how its disruption contributes to disease states.