The goal of the work is to clarify the neuroanatomical organization and neurotransmitter content of circuits in the brain that help maintain homeostasis through visceral responses and motivated (goal-oriented) behavior. Detailed experimental pathway tracing studies have been carried out over the last 12 years in the rat with axonal transport and immunohistochemical methods. The results have greatly clarified the longer connections of cell groups in many parts of the limbic region and hypothalamus, parts of the brain known to play a critical role in maintaining homeostasis and preserving the species through reproductive physiology and behavior. The work is designed to supply detailed information about one of the most functionally important aspects of this circuitry that remains poorly understood at this time; namely, the organization of intrahypothalamic connections. The hypothalamus consists of 3 longitudinal zones; a periventricular zone that contains at least 7 distinct groups of neuroendocrine motoneurons, and 2 distinct groups of preautonomic neurons; a medial zone of nuclei that receives massive inputs from the limbic region of the telencephalon; and a lateral zone that gives rise to massive though diffuse projections to the cerebral cortex, spinal cord, and many regions in between. It is hypothesized that each nucleus of the medial zone gives rise to a highly organized series of projections to the periventricular zone, lateral zone, and other nuclei of the medial zone, and that together the medial zone nuclei may act at a """"""""central pattern generator"""""""" involved in the integration of neuroendocrine, autonomic, and behavioral responses vital for the survival of the individual and the species as a whole. This approach has been made possible by the recent development in this laboratory of what amounts to an experimental Golgi method for tracing the projections from a small group of neurons injected with the lectin Phasiolis vulgaris leukoagglutinin (PHA-L). The advantages of the method are that PHA-L is not taken up by fibers-of-passage, is transported only in the anterograde direction, is extremely sensitive, labels axons with the clarity of a Golgi impregnation, and can be visualized readily at both the light and EM levels. Specifically, it is proposed to examine experimentally the projections of the medial preoptic, anterior hypothalamic, ventromedial, dorsomedial, and premammillary nuclei to particular components of the periventricular and lateral zones at the light level, and to confirm the terminal fields of the medial preoptic nucleus ultrastructurally. These studies will lay the necessary groundwork for future investigations of collateralization and neurotransmitter content in these integrative pathways.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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Salk Institute for Biological Studies
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Hahn, Joel D; Swanson, Larry W (2012) Connections of the lateral hypothalamic area juxtadorsomedial region in the male rat. J Comp Neurol 520:1831-90
Canteras, Newton S; Ribeiro-Barbosa, Erika Renata; Goto, Marina et al. (2011) The retinohypothalamic tract: comparison of axonal projection patterns from four major targets. Brain Res Rev 65:150-83
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
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) 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
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
Simmons, Donna M; Swanson, Larry W (2008) High-resolution paraventricular nucleus serial section model constructed within a traditional rat brain atlas. Neurosci Lett 438:85-9
Bota, Mihail; Swanson, Larry W (2007) Online workbenches for neural network connections. J Comp Neurol 500:807-14
Dong, Hong-Wei; Swanson, Larry W (2006) Projections from bed nuclei of the stria terminalis, magnocellular nucleus: implications for cerebral hemisphere regulation of micturition, defecation, and penile erection. J Comp Neurol 494:108-41

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