Parker Lab Research
The Dopamine System
Midbrain dopamine neurons innervate the striatum, the input stage of the basal ganglia circuit. Our lab determines how multicellular activity in the striatum is sculpted in space and time and how this process becomes altered during learning and disease.
Specifically, we focus on the principal neurons of the striatum: D1- and D2- dopamine receptor-expressing spiny projection neurons (SPNs). These neurons normally have balanced levels of activity and co-activate in spatially overlapped clusters.
We know that these D1- and D2-SPN dynamics are perturbed under conditions modeling diseases like Parkinson’s and schizophrenia. Our goal is to identify the biological factors that constrain these dynamics so that we might intervene, pharmacologically, to normalize them in disease.
Parker Lab Research
Approach
We perform large-scale recordings of striatal activity and neurotransmitter signaling using miniaturized fluorescence microscopes and two-photon microscopy.
We combine these tools with viral genetic and pharmacological manipulations in healthy animals and animal models of neuropsychiatric diseases to better understand both normal and aberrant striatal function.
Miniaturized Fluorescence Microscopy
Two-Photon Fluorescence Microscopy
Parker Lab Research
Findings
Using these tools, we have found that the levels and spatially clustered dynamics of D1- and D2-SPN activity are distinctly perturbed under conditions modeling Parkinson’s disease and schizophrenia.
Work is underway to determine how endogenous neuromodulation constrains these dynamics and how pharmacologic interventions influence this process to ameliorate disease symptoms.
