Precise Tracing and Manipulation of Striosomal Circuits

Grant Type
Basic
Grant Year
2004-2005
Institution Location
GA
Institution Organization Name
Emory University
Investigators Name
Ciliax, Brian, PhD

The ultimate goal of this project is to determine the role of a very specific brain region in the regulation of dopaminergic neurons of the brainstem; a circuit that may be important for learning new movements and “unlearning” unwanted movements in TS. The brain region in question is a compartment within a larger brain region called the striatum and it consists of numerous “patches”. Complicated studies have indicated that the neurons in the patches send axons (long, thin extensions that connect to other neurons) directly to these dopaminergic neurons. However the inability to study patch neurons in isolation from neurons in the surrounding “matrix” compartment has made definitive tracing and functional studies very difficult. The immediate goal of this research is to develop the tools that will enable us to trace and control the firing rate of the patch neurons. This will be accomplished by introducing transgenes (foreign or altered genes) into the striatum using lentivirus as a vector deliverer. Although the virus will infect all neurons in the injection site, the transgenes will be expressed only by neurons in the patch since their promoters (the stretch of DNA just before the gene sequence that determines when and where that gene is expressed in the animal’s body) will be specific for the µ opiate receptor which is selectively made by patch neurons. In this way we will be able to express mutant “G-proteins” that control the firing rate of neurons in the patch but not in neurons of the surrounding matrix. These tools will allow us to study neurons in the patch in isolation, eliminating confounding effects by the matrix neurons and leading to a rapid and precise characterization of the specific circuits of the patches that control dopaminergic neurons. Brian Ciliax Ph.D. Emory University School of Medicine, Atlanta, GA Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2004-2005