UNC Alcohol Research Center
Primary Investigator: Dr. Clyde Hodge
Co-Investigator: Dr. Ian Shih
The primary goal of the UNC Alcohol Research Center (ARC) is to increase understanding of the molecular and cellular pathogenesis in alcohol use disorder (AUD). To facilitate this goal, the Research Components propose to evaluate changes in neurocircuit function that drive pathological brain and behavioral processes. The purpose of the Scientific Resource Core (SRC) is to facilitate and extend this integrated research effort by providing access to cutting-edge technology, shared facilities, resources, and technical expertise for analysis of alcohol-induced changes in neural circuit activity, connectivity, and evaluation of localized changes in gene and protein expression. In addition, the SRC fosters interaction among ARC investigators with the explicit purpose of increasing coordination and cohesiveness among individual research components. The Specific Aims are:
Aim 1. Provide facilities, resources, and expertise for analysis of rodent functional neural networks. A primary goal of the ARC is to evaluate the activity of specific neural circuits in alcohol-related cellular and behavioral pathologies. To support this effort, SRC will provide resources and expertise to support a multi-year collaborative rodent functional connectivity MRI (fcMRI) analysis combined with magnetic resonance spectroscopy (MRS) in rats to evaluate alcohol-induced changes in regional brain connectivity and transmitter reserve in regions of interest. A second goal of the ARC is to evaluate the hypothesis that alcohol-induced pathology is associated with disrupted balance between excitatory and inhibitory transmission (E/I balance) in specific brain regions and neural circuits studied by ARC research components. To support this effort, the SRC will provide equipment and expert support for a novel multi-spectral, four-channel fiber photometry platform to measure genetically encoded calcium activity in excitatory and inhibitory neurons. Together, these highly innovative fcMRI / MRS and photometry technologies provide a unique platform for ARC Research Components to evaluate the impact of alcohol use on mechanistic activity within functional neural networks.
Aim 2. Provide facilities and resources for evaluation of changes in gene and protein expression, and circuit function in specific rodent brain regions. ARC Research Components propose rigorous assessments of alcohol-induced changes in synaptic activity, and protein and gene expression in specific rodent brain regions and neural circuits. To facilitate this shared goal, the SRC will provide: 1) facilities and resources for standard and fluorescence immunohistochemistry, Western/immunoblots, and RT-PCR; 2) access to modern light, wide-field, and laser scanning confocal microscopes; 3) access to electrophysiology and optogenetic equipment and resources; and 4) equipment maintenance. The Core also provides full access to state-of-the-art software and equipment for quantitative analysis and presentation of digital images. Findings will be archived on a centralized server for data sharing and integration.
Aim 3. Facilitate collaborative and integrative research efforts of the ARC. A primary goal of the SRC is to increase coordination and cohesiveness among the individual research projects. This objective is accomplished at one level by evaluation of overlapping mechanisms and brain regions, shared resources and specific methods listed above. The purpose of this aim is to explicitly promote collaboration and integration. To accomplish this goal, we will hold monthly SRC meetings to allow PD/PI and trainee presentation of key findings, discuss barriers in the field and how to apply new and innovative strategies, provide a venue for ongoing administrative review of progress, and assure that the SRC continues to be a dynamic resource that evolves to meet ARC Research Component needs.
Overall, the centralized services and specialized equipment provided by the SRC will:
- Provide significant ongoing support for the vibrant alcohol research environment at UNC Chapel Hill.
- Afford ARC investigators the opportunity to employ innovative, cutting-edge technologies that are novel to their specific research programs in a quality-controlled, expert-supported environment. This critical aspect of the Core broadens both the individual and integrated scope of the ARCâ€™s research efforts.
- Play a critical role in successful completion of the research projects in an efficient and effective manner.
- Generate significant cost savings to the ARC by reducing redundancies in equipment, supplies, and personnel.
- Serve a major integrative role by providing shared methodologies and a formal venue in which investigators can present and discuss findings of the Research Components and plan new directions.