1985 — 1989 |
Miselis, Richard R |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Circumventricular Organs--Modulators of Homeostasis @ University of Pennsylvania
As circumventricular organs, the subfornical organ (SFO), situated at the front of the brain, and the area postrema (AP), located at the rear of the brain, lack a blood-brain barrier making them putative central receptor sites for humoral factors affecting behavioral and physiological controls of homeostasis. Each has efferent neural projections enabling them to affect brain function. The SFO primarily affects preoptichypothalamic function and the AP primarily affects relays for ascending visceral afferent information. The first major objective of this grant is to determine the functional roles of the neural components of the projections of the SFO and AP in behavioral, neuroendocrine and physiological controls of water and salt balance. Microtransections, microlesions and aspiration lesions will be used to interrupt specific elements of the neural circuitry and the preparations will be analyzed for specific and general deficits in behavioral and physiological control mechanisms. These preparations will be given individual challenges and their drinking responses followed over the short and long term while monitoring urine output and plasma parameters to assess alterations in internal state. The second major objective is to continue neuroanatomical studies of the neural connectivity of the SFO, AP, and the nucleus of the solitary tract using conjugates of horseradish peroxidase, fluorescent dyes and tritiated amino acids as tracers. Particular attention will be given to the size and location of the afferent sources to the SFO and AP in comparison to the size and destination of their efferent projections. This research will further our understanding of basic mechanisms of thirst and homeostasis and will provide insights into the neural circuitry coordinating behavioral, neuroendocrine and autonomic controls of homeostatic function. It focuses on simple pathways, some between higher forebrain mechanisms and lower brainstem areas receiving direct visceral afferent input. It emphasizes behavioral controls but does not neglect physiological mechanisms to avoid mistaken interpretations of behavioral changes. This multidisciplinary research will better enable understanding of complex health related problems such as hypertension, essential hypernatremia, syndrome of inappropriate antidiuretic hormone secretion and psychogenic polydipsia.
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1990 — 1993 |
Miselis, Richard R |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Visceral Neuraxis in Homeostasis @ University of Pennsylvania
The visceral neuraxis of the mammalian brain is a network of neural connections that mediates the behavioral and physiological controls of homeostasis. It can be defined neuroanatomically by its connections to the autonomic nervous system, connections with circumventricular organs of the brain and connections to the major hypothalamic nuclei affecting endocrine function as well as by interconnections of intervening nuclei. The circumventricular organs, which lack a blood brain barrier making them putative central receptor sites for humoral factors affecting visceral function, and the visceral afferents (chemoreceptors, baroreceptors and mechanoreceptors) of the peripheral nervous system make up the sensory side of the network. The motor components are the autonomic nervous system, endocrine system and homeostatic behavior. The long term objectives of this project are to define and understand the operation of the components of the visceral neuraxis contributing to the generation of ingestive behaviors and specific behavioral states and the factors which convert them into health damaging behaviors or states that accompany obesity, schizophrenia, hypertension, psychogenic polydipsia, stress ulcers, and essential hypernatremia. The first specific objective is to complete the viscerotopic mapping and immunocytochemical characterization of the brainstem's innervation of organs of the alimentary canal. Neuroanatomical studies (single and double labeling) at the light and electron microscopic level will be done using conjugates, particularly cholera toxin, of horseradish peroxidase, fluorescent dyes, dye tagged lectins, toxins and antibodies to neuropeptides. The goal is to determine how incoming visceral afferent information is routed and modified by neuropeptides for local control of viscera and for influencing behavior. The second goal is to determine at the ultrastructural level how gastric afferents which presumably play a role in satiation distribute to neurons that project up the visceral neuraxis and to neurons that remain connected locally. The third goal is to determine at the ultrastructural level using a double labeling technique how descending projections from the hypothalamus to the vagal complex influence the input and processing of visceral afferent information through the visceral neuraxis for use in behavior. The fourth goal is to determine the effects of microlesioning pathways and terminal field sites of new projections from the subfornical organ on drinking behavior and renal function in response to thirst challenges.
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1992 — 1998 |
Miselis, Richard R |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Visceral Neuraxis in Homeostasis @ University of Pennsylvania
The visceral neuraxis of the mammalian brain is a network of neural connections that mediates the behavioral and physiological controls of homeostasis. It can be defined neuroanatomically by its connections to the autonomic nervous system, connections with circumventricular organs of the brain and connections to the major hypothalamic nuclei affecting endocrine function as well as by interconnections of intervening nuclei. The circumventricular organs, which lack a blood brain barrier making them putative central receptor sites for humoral factors affecting visceral function, and the visceral afferents (chemoreceptors, baroreceptors and mechanoreceptors) of the peripheral nervous system make up the sensory side of the network. The motor components are the autonomic nervous system, endocrine system and homeostatic behavior. The long term objectives of this project are to define and understand the operation of the components of the visceral neuraxis contributing to the generation of ingestive behaviors and specific behavioral states and the factors which convert them into health damaging behaviors or states that accompany obesity, schizophrenia, hypertension, psychogenic polydipsia, stress ulcers, and essential hypernatremia. The first specific objective is to complete the viscerotopic mapping and immunocytochemical characterization of the brainstem's innervation of organs of the alimentary canal. Neuroanatomical studies (single and double labeling) at the light and electron microscopic level will be done using conjugates, particularly cholera toxin, of horseradish peroxidase, fluorescent dyes, dye tagged lectins, toxins and antibodies to neuropeptides. The goal is to determine how incoming visceral afferent information is routed and modified by neuropeptides for local control of viscera and for influencing behavior. The second goal is to determine at the ultrastructural level how gastric afferents which presumably play a role in satiation distribute to neurons that project up the visceral neuraxis and to neurons that remain connected locally. The third goal is to determine at the ultrastructural level using a double labeling technique how descending projections from the hypothalamus to the vagal complex influence the input and processing of visceral afferent information through the visceral neuraxis for use in behavior. The fourth goal is to determine the effects of microlesioning pathways and terminal field sites of new projections from the subfornical organ on drinking behavior and renal function in response to thirst challenges.
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