The Scripps Research Institute Alcohol Research Center

The Scripps Research Institute ARC

TSRI ARC

Cellular Neurobiology

Director: Marisa Roberto, Ph.D.

The Cellular Neurobiology Research Component will focus on the overall hypotheses that the transition from low levels of drinking to chronic binge drinking is driven by decreased activity in opioid and eCB systems in “reward circuits” in the amygdala and that the transition from binge drinking to dependence is driven not only by compromised function in reward systems but a recruitment of a dysregulated central stress system driven by CRF in the extended amygdala. Amygdala slice preparations will be used to functionally and morphologically characterize central nucleus of the amygdala (CeA) and basolateral amygdala (BLA) neurons (Specific Aims 1 and 2) and neurocircuitry (Specific Aims 1-3) involved in responses to ethanol, CRF, and cannabinoids in the progression from binge drinking to dependence. Specific Aim 1 is designed to test the hypothesis that binge drinking or dependence will differentially alter responses to cannabinoids (CB1 receptor agonists and antagonists) in specific neuron types in the BLA and CeA. Specific Aim 2 is designed to test the hypothesis that withdrawal from alcohol binging or dependence will alter synaptic glutamatergic transmission both within and between the BLA and CeA or membrane properties or their responses to CRF and acute ethanol via changes in Narp levels. Specific Aim 3 is designed to use tracing via retrograde labeling from brain region targets of BLA and CeA neurons, such as the BNST, VTA, and PFC, to test the hypothesis that alterations in synaptic properties within specific neurocircuitries are involved in binge drinking, dependence, and withdrawal and may be associated with changes in the eCB and CRF systems. This project will involve collaborations with the Zorrilla Component and Viral Vector, Animal Models, and Biochemical Cores.