It has been well established that alcohol can modulate a variety of molecular targets resulting in changes in synaptic function and circuit activity. Much of this body of work has focused on relatively high alcohol concentrations, leaving a gap in knowledge regarding the molecular and circuit targets of low dose alcohol. This is a critical topic, as a mechanistic understanding of these highly sensitive targets can provide an opportunity to probe how alcohol initially impacts the brain. Because of the limited data on the neuronal circuits sensitive to low dose alcohol, we are electing to approach this problem using primarily unbiased anatomical approaches. Specifically, leveraging expertise of multiple laboratories, we will capitalize on cutting edge molecular approaches and advances in whole-brain in vivo imaging to identify and interrogate highly conserved neuronal circuits and molecular targets that are sensitive to low dose alcohol. We will then use converging approaches to test the causal role of these circuits and molecules in regulating sensitivity to low dose alcohol. Therefore, taken together, these aims will provide an unprecedented opportunity to identify (Aims 1 and 2) and test the causal role (Aim 3) of brain circuits and molecules that are activated by low dose alcohol.

Public Health Relevance

It has been well established that high doses of alcohol can modulate a variety of molecular targets resulting in changes in synaptic function and circuit activity. However, less is known regarding the molecular and circuit targets of low dose alcohol. As such, experiments in this proposal will use a variety of techniques to identify and test the causal role of brain circuits and molecules that are activated by low dose alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA025582-01
Application #
9265683
Study Section
Special Emphasis Panel (ZAA1-JJ (08)R)
Program Officer
Powell, Elizabeth
Project Start
2016-09-01
Project End
2021-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$380,000
Indirect Cost
$130,000
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Kao, Yu-Chieh Jill; Oyarzabal, Esteban A; Zhang, Hua et al. (2017) Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke: A Multimodal Magnetic Resonance Imaging Study. Stroke 48:754-761
Van Den Berge, Nathalie; Albaugh, Daniel L; Salzwedel, Andrew et al. (2017) Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI. Neuroimage 146:1050-1061
Hwa, Lara; Besheer, Joyce; Kash, Thomas (2017) Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective. F1000Res 6:298