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.
Showing the most recent 10 out of 81 publications
