Studies Of Central Nervous System Functional Anatomy

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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, infectious disease, and drug abuse. 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 deletions (transgenic mice) or that are subjected to stress, inflammatory stimuli, or infections. 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. Key anatomical pathways and relevant neurotransmitter/receptor systems are mapped using histochemical techniques. In situ hybridization histochemistry (ISHH) 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 activation of class I major histocompatibility complex (MHC) mRNA in both neuronal and non-neuronal cells under conditions of immune and non-immune physiological challenges, 2) cataloged immune system mRNA expression level changes in the hippocampus and frontal cortex of rats given a single electroconvulsive shock, 3) mapped activin and brain-derived neurotrophic factor (BDNF) mRNA induction in the kindling model of epilepsy, 4) characterized the role of toll-like receptors (TLR4) in the peripheral hematopoietic versus central (non-hematopoietic) compartments in mediating the CNS response to peripheral lipopolysaccharide (LPS) challenge, and 5) 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. Current work examines the role of other TLRs in detecting pathogen-associated molecules and alerting the brain about peripheral immune challenges. We are also continuing work aimed at defining the role that the NF-kB transcription factor plays in anxiety-like behavior and in response to stressors.