The long-term goal of this study is to identify the neural machinery that controls homeostatic processes. Many of these functions involve a network of neuroendocrine and autonomic components located in the hypothalamus and amygdala, which in conjunction with brainstem effector mechanisms, mediate the adaptive response to physiological demands. Central to the adaptive response of these neurons is their ability to modify protein synthesis and thereby the chemically-coded information contained within neurons. Since the regulation of mRNA levels is central to the process used by neurons to control the synthesis of neuromodulators and transmitters, any stimulus that modulates mRNA levels is in a position to alter neuronal function. The hypothesis to be tested is that in order to mediate the appropriate response to diverse stimuli the homeostatic process requires modification of the chemically-coded information contained within neurons through the modulation of mRNA levels. Experiments will focus on 2 contrasting physiological stressors, osmotic stimulation and ether anesthesia. They will explore the mechanisms that regulate the response of peptide-coding mRNAs in 4 regions intimately involved with the homeostatic process; the hypothalamic paraventricular (PVH), supraoptic (SO) nuclei, lateral hypothalamic area (LHA) , and central nucleus of the amygdala (CeA). These regions provide vital contributions to the neuroendocrine and autonomic aspects of homeostatic regulation. The response of neuronal mRNAs to the 2 stimuli will be assessed by semi-quantitative in situ hybridization histochemistry (ISH). ISH is ideally suited to determining the magnitude and direction of changes in mRNA levels at precise anatomical loci, and is also compatible with other current anatomical techniques. The mechanisms will be addressed in 3 experiments. 1), dose/response determinations will consider the. dynamic aspects of system. 2), exogenously manipulated plasma corticosterone Will begin to address the role of humoral inputs. 3), measuring the effects of lesions in areas known to provide afferents to the 4 regions will address the role of neural inputs. Further experiments will explore the circuits by which altered chemically-coded signals may be transmitted to target sites. Here ISH is combined with the retrogradely transported fluorescent dyes injected into potential target areas. The timing of this study represents a logical extension of past neuroanatomical and physiological studies, and should provide the basis for future studies on the specific mechanisms that determine how the brain controls these important homeostatic mechanisms in health and disease.
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