Bird, Devin; Nufer, Teresa; Wu, Bridget; Edwards, Jeffrey (Brigham Young University)
Faculty Advisor: Edwards, Jeffrey (Brigham Young University, Physiology and Developmental Biology)
Drug addiction is a consequence of neural plasticity in the ventral tegmental area (VTA), an area of the brain's reward system, in which higher levels of dopamine are expressed. Research suggests that decreased activity of inhibitory _-aminobutyric acid (GABA) neurons in the VTA could be the cause of increased activity of dopaminergic cells in the VTA, and thus mediate opiate addiction (Tan). However, not much additional research has been performed to evaluate the plasticity of VTA GABA neurons and the role they play in addiction. Why are VTA GABAergic cells being inhibited and how? We hypothesize that inhibitory inputs onto GABA neurons in the VTA directly affect the degree of inhibition of VTA dopaminergic cells. Additionally, we hypothesize that GABAergic neurons of the lateral hypothalamus (LH) is a source input that extends into the VTA and inhibits VTA GABAergic neurons. We believe that inhibition from these LH neurons induces plasticity of VTA GABAergic neurons.
Through the use of optogenetics we have been able to isolate precise GABAergic pathways that lead into the VTA. Specifically, we have isolated input sources from the LH. These optogenetic experiments, in combination with electrophysiology, have allowed us to measure the specific effects that LH GABA neurons have on VTA GABA neurons. Currently, our data suggests that LH GABAergic cells do induce long-term depression (LTD) in VTA GABAergic cells, however, it is too soon to make any conclusions. Although experiments are still underway, we believe that LH GABAergic neurons play an important role in the drug addiction pathway by inhibiting VTA GABAergic neurons and inducing plasticity.