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.
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.
|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|