The Section on Functional Neuroanatomy combines molecular and neuroanatomical methods to identify dynamic aspects of nervous system function that relate to issues of mental health and neuroimmune pathophysiology. The current objective of our laboratory is to explore the interaction between the central nervous system (CNS) and the immune system in animals that have selective gene modifications (knockout or transgenic mice) and that are subjected to stress, fear paradigms, seizures, or inflammatory stimuli. Our approach is to clarify the normal and pathophysiological roles of immune system molecules in the brain, to identify cellular and molecular components induced by immunological challenges, and to further characterize the responses at molecular, anatomical, and functional levels. A recent focus is on the role of a transcription factor called NF-kappaB (NF-kB) in neuronal function. NF-kB is found in all cells but is normally associated with immune cell function, regulating inflammation, apoptosis, or survival. However its presence in neurons suggests other roles, possibly related to cell survival or neuronal plasticity. Tools are being designed to measure NF-kB exclusively in neurons in vivo and to show genes regulated by it in models of neuronal excitation and excitotoxicity. Key anatomical pathways and relevant neurotransmitter/receptor systems are mapped using histochemical techniques. In situ hybridization histochemistry is used to localize and quantify mRNA expression of neurotransmitters, cytokines, enzymes, receptors, transcription factors, and immediate-early genes in studies of adaptive changes to immunological, pharmacological, physiological, behavioral, or surgical manipulations. Immunohistochemistry and double-label techniques are used to characterize the phenotypes of the cells that show induced mRNA expression of immune signaling molecules. We have 1) shown for the first time that the p50 subunit of the NF-kB transcription factor is involved in normal expression of emotional behavior in mice, 2) shown that another transcription factor TIF-2, a coactivator of the glucocorticoid receptor, is necessary for normal adrenocortical development and biosynthesis and hypothalamic-pituitary-adrenal axis function, and 3) found a phosphorylation state of the p65 subunit of NF-kB that can serve as a reliable index of neuronal NF-kappa activity. Current work examines role that the NF-kB transcription factor plays in anxiety-like behavior, fear learning, and response to stressors. Primary cell cultures are used to examine neuronal genes regulated by the NF-kB transcription factor in an activity-dependent manner.
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