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 alcoholism. To address this goal, the Research Components propose to evaluate changes in gene and protein expression, behavior, and neurocircuit function that span the spectrum of alcohol-related pathologies. 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 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 of the SRC are:
Aim 1. Support functional connectivity magnetic resonance imaging (fcMRI) studies to discover novel alcohol-induced changes in rat and mouse neural circuit connectivity spanning multiple phases of addiction. A primary goal of the UNC ARC is to evaluate the mechanistic involvement of specific neural circuits in alcohol-related cellular and behavioral pathologies. To complement and extend this mechanistic effort, the SRC will support a center-wide preclinical fcMRI analysis of alcohol-induced changes in brain regional connectivity. Five separate fcMRI studies (one for each Research Component) will assess alcohol-induced changes in functional connectivity, and activity, associated with multiple phases of addiction in rat and mouse models. Functional connectivity analyses will be performed on seed regions that integrate the research components, including amygdala, nucleus accumbens, prefrontal cortex, insular cortex, and dorsal striatum. Rodent connectivity data will be compared, qualitatively, to human MRI data from Component 3 to assess conservation of changes across mammalian species and animal models. This translational approach has unique potential to transform our understanding of how neural circuit connectivity is altered during conditions of escalating exposure severity associated with alcohol addiction.
Aim 2. Provide facilities and resources for standardized assessments of changes in protein and gene expression, and circuit function in specific rodent brain regions. The UNC ARC Research Components propose rigorous assessments of alcohol-induced changes in 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 quantitative 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.
Together, these services and resources provide the Research Components with the unique capability of delineating alcohol-induced molecular changes in specific brain regions that are associated with altered neural circuit connectivity. Further, by integrating mechanistic approaches in rodents, that activate specific circuits, the fcMRI approach has potential to transform understanding of the maladaptive changes in neural circuitry that underlie alcohol addiction. Moreover, this innovative and integrative strategy represents a clear advantage to conducting the proposed research as a center rather than separate research efforts, exactly the goal of an NIAAA ARC SRC.
A main function of the SRC is to increase coordination and cohesiveness among the research projects. To accomplish this additional goal, the SRC holds a monthly meeting during which ARC investigators present key findings of the individual research components, review SRC functions and progress, and keep staff up-to-date regarding new or outdated needs. Moreover, these meetings provide a critical venue for Administrative review of progress and assure that the SRC remains dynamic and evolves to meet research component needs.
Overall, the centralized services and specialized equipment provided by the SRC will:
- Afford investigators the opportunity to employ cutting-edge technologies that are novel to their specific research programs (e.g., fcMRI) in a quality controlled, expert-driven environment. This important aspect of the Core broadens both the individual and integrated scope of the ARC’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.