The theme of this proposed Botanical Dietary Supplement Research Center (BDSRC) are to define the molecular and cellular mechanisms by which bioactive botanicals may beneficially promote psychological resilience in the context of social defeat (Project 1), preserve cognitive function in the context of sleep deprivation (Project 2), and to develop probiotic supplements that can optimize the utilization of these specific botanicals (Project 3), with the final goal to develop bioactive botanicals with defined mechanisms of action for immediate application in humans. Critical to this goal are objective measures of the biological effects of the botanical supplements on brain function in the context of chronic social defeat and sleep deprivation. Core C will support the overall goals of the BDSRC by facilitating preclinical behavioral testing and electrophysiology analysis. The Behavioral Phenotyping Component will use multiple behavioral measures to determine how botanical supplements affect behavioral functioning. Following an initial assessment designed to exclude any significant motor or sensory deficits that would confound interpretation of more complex tests, chronic social defeat stress and social avoidance (social interaction) test will be performed for Project 1. For Project 2, a series of behavioral tests will be administered that will emphasize the core behavioral features of memory dysfunction. Testing will include assays to detect anxiety related behavior as well as tests designed to measure learning and memory related functions, including the Morris water maze, contextual and cued fear conditioning, a Y-maze working memory task, and a novel object recognition task. The Electrophysiology Component will measure excitatory and inhibitory synaptic plasticity in the nucleus accumbens (NAc) to dissect the mechanistic role of phenolic metabolites on promotion of resilience to chronic social stress (Research Project 1). The Electrophysiology Component will also measure synaptic plasticity in the hippocampal formation to assess the role of phenolic metabolites on cognitive function in the context of acute and chronic sleep deprivation (Research Project 2). Collectively Core C will support the goals of individual projects by providing objective measures that will allow the biological effects of botanical supplements to be correlated with synaptic activity and function. Core C will also provide toxicology analysis for safety profiles for preclinical in vivo studies.
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