About WeiXing Shi, PhD
My research interests are in the neurobiology and pharmacology of brain disorders including schizophrenia, Parkinson’s disease, ADHD, and drug addiction. We use a wide range of research techniques including in vivo and in vitro electrophysiological recording, optogenetics, chemogenetics, and fiber photometry.
One focus of my research has been on midbrain dopamine (DA) neurons. These neurons project to various forebrain areas, forming the so-called nigrostriatal, mesolimbic, and mesocortical DA pathways. Degeneration of the nigrostriatal DA pathway causes Parkinson’s disease, whereas dysfunction of the mesolimbic and mesocortical DA systems has been implicated in psychiatric disorders including schizophrenia, depression, ADHD, and drug addiction. The goal of my research is to understand how the activity of DA neurons is regulated in the brain and affected by drugs such as amphetamine and L-DOPA. We have shown that amphetamine and related psychostimulants, but not L-DOPA, excite DA neurons via adrenergic α1 receptors. This finding may explain why in DAT-knockout animals, amphetamine and cocaine remain addictive and can still increase DA release.
The other focus of my research is on the prefrontal cortex (PFC), a key structure involved in the executive functions of the brain including decision making, attention, and impulse control. Evidence suggests that the PFC regulates DA neurons and plays crucial roles in the same disorders that DA neurons have been implicated in. Evidence also suggests that amphetamine acts through the PFC to excite DA neurons to increase DA release. We have shown that psychostimulants, but not L-DOPA, promote a cortical state known as the Up state which is essential for arousal and attention. Our evidence further suggests that the Up-state promoting effect of psychostimulants is largely mediated through adrenergic α1 receptors.
Anatomical evidence suggests an interaction between DA and PFC neurons. Supporting this suggestion, we have provided the first evidence that the activity of DA neurons is correlated, on a subsecond timescale, with the activity of PFC neurons. More importantly, we have shown that this functional coupling between DA and PFC neurons can be significantly altered by drugs. We are investigating the pathways mediating the functional coupling between DA and PFC neurons.