The long-term objective of the proposed work is to identify and characterize at high resolution the structure and chemistry of neural circuits in the mammalian brain that underlie the basic drives and emotions keeping individuals alive and assuring survival of the species associated with hunger and thirst, defensive (fight or flight) behavior, reproductive (sexual and parental) behavior, and the sleep/wake cycle. Previous work identified the hypothalamus as a critical node in this circuitry, and characterized in detail axonal input/output relationships of its medial half with the pituitary gland, cerebral hemispheres, and brainstem/spinal cord. The proposed work is designed to complete in a systematic way, and to extend, a similar analysis of the lateral hypothalamus, and is based on the hypothesis that the lateral hypothalamus consists of two fundamentally different components, a dorsal region with widespread, diffuse projections to much of the central nervous system, and a surrounding compartmentalized region divided into some two dozen parts with very specific projection patterns to specific functional systems. The three specific aims are, a) to complete a phase one, regional analysis of the surrounding compartmentalized region;b) to begin a phase two, neuronal cell type analysis, starting with certain lateral hypothalamic regions apparently involved critically in food appetite regulation;and c) to facilitate the entry of neuroanatomical data into neuroinformatics workbenches on the web. The research is based on the combined use in rats of experimental intra-axonal pathway tracing methods, and hybridization histochemistry for the cell type-specific expression of neurotransmitter-related genes. There is a rich clinical and experimental history, dating back over a century, that disturbances of the hypothalamus, and parts of the brain interacting with the hypothalamus, produce depending on localization either obesity or anorexia, profound effects on cardiovascular and endocrine (for example, blood glucose) measures, anxiety and mood, aggressive behavior, sexual behavior and physiology (for example, the menstrual cycle), and disturbances of normal sleep and wakefulness patterns. The proposed research is designed to clarify very poorly understood neural circuits that mediate normal ingestive, defensive, reproductive, and sleep/wake behaviors;understanding their pathology will follow.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Method to Extend Research in Time (MERIT) Award (R37)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Gnadt, James W
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University of Southern California
Schools of Arts and Sciences
Los Angeles
United States
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Brown, Ramsay A; Swanson, Larry W (2013) Neural systems language: a formal modeling language for the systematic description, unambiguous communication, and automated digital curation of neural connectivity. J Comp Neurol 521:2889-906
Hahn, Joel D (2010) Comparison of melanin-concentrating hormone and hypocretin/orexin peptide expression patterns in a current parceling scheme of the lateral hypothalamic zone. Neurosci Lett 468:12-7
Hahn, Joel D; Swanson, Larry W (2010) Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat. Brain Res Rev 64:14-103
Simmons, Donna M; Swanson, Larry W (2009) Comparison of the spatial distribution of seven types of neuroendocrine neurons in the rat paraventricular nucleus: toward a global 3D model. J Comp Neurol 516:423-41
Dong, Hong-Wei; Swanson, Larry W; Chen, Lin et al. (2009) Genomic-anatomic evidence for distinct functional domains in hippocampal field CA1. Proc Natl Acad Sci U S A 106:11794-9
Simmons, Donna M; Swanson, Larry W (2009) Comparing histological data from different brains: sources of error and strategies for minimizing them. Brain Res Rev 60:349-67
Cenquizca, Lee A; Swanson, Larry W (2007) Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res Rev 56:1-26
Swanson, Larry W; Grant, Gunnar; Hokfelt, Tomas et al. (2007) A century of neuroscience discovery: reflecting on the Nobel Prize awarded to Golgi and Cajal in 1906. Brain Res Rev 55:191-2
Swanson, Larry W (2007) Quest for the basic plan of nervous system circuitry. Brain Res Rev 55:356-72
Bota, Mihail; Swanson, Larry W (2007) Online workbenches for neural network connections. J Comp Neurol 500:807-14

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