P/F Project 2: “Determining fluctuations in the striatal transcriptome following distinct dopaminergic activation mechanisms” (PI: Ali D. Güler, PhD, Assistant professor, Department of Biology, University of Virginia)

Specific Aims.   Dr. Güler is a new investigator at the University of Virginia, Department of Biology. The Güler lab is working to uncover how the brain navigates through a perplexing wealth of information for the proper selection of behavioral outcomes by focusing on neural circuits that govern goal-directed behaviors like feeding or drug-seeking. The PI is aiming to rationally determine treatment targets against neurological disorders by delineating specific neural networks at both anatomical and the molecular level. PI has developed a conditional transgenic mouse model that rapidly and reversibly elevates neural activity of a genetically defined population of neurons without requiring invasive techniques. This model utilizes selective expression of the capsaicin receptor, TRPV1, on an otherwise trpv1 null background. Using the model to express TRPV1 from dopaminergic neurons, the Güler lab is currently performing in vivo electrophysiology in awake and behaving mice in combination with standard molecular and biochemical techniques to determine the role of dopaminergic system and its downstream targets in goal-directed behaviors. Additionally, the Güler lab is interested in how and why some dopaminergic drugs lead to addiction while others do not. In the present P/F project, he proposes two specific aims:

Aim 1: To determine differences in expression profile of striatal neural populations following short- or long-term administration of drugs that elevate dopamine levels via distinct mechanisms.

Aim 2: To manipulate genes that are differentially regulated by dopaminergic drugs with molecular and pharmacological techniques during behavioral paradigms to ascertain their role in goal-seeking behavior.