Viral Mediated Gene Transfer (Transgenic Core)
This involves the use of recombinant viruses to express a protein in a localized region of brain. We engineer herpes simplex virus (HSV) or adeno-associated virus (AAV) vectors to express stress-regulated protein, or an inhibitor of that protein. These viral vectors are injected into a brain reward region (e.g., VTA or NAc), where they infect only neurons and express the encoded protein in a highly circumscribed region of brain (Figure 9). By overexpressing the protein, and by expressing an inhibitor of the protein, it is possible to both mimic and block the drug- and stress-induced change. One innovation of our Center has been to use viral vectors to express small inhibitory RNA’s (so-called RNAi) which suppress the activity of targeted messenger RNA’s in the brain. Viral-mediated gene transfer is used in both rats and mice, and examples can be found in each of the Projects.