The use of cFos as a neuronal activity marker has provided important insights into hypothalamic and autonomic integration that will be investigated further in this renewal application. Although much has been learned about how cFos expression reflects activation defined in terms of hormone or transmitter release, left unresolved is the question of whether cFos expression in hypothalamic neurons is linked to transcriptional upregulation as well. Advances in molecular biology now make possible a more intensive investigation of the consequences and correlates of cFos expression in terms of transcriptional events. Studies of magnocellular neurons will use these advances to evaluate the hypothesis that cFos expression is coupled with general transcriptional activation in magnocellular neurons, whether or not stimulated neurosecretion occurs. This will be accomplished by study of the relations between cFos induction, pituitary secretion of AVP or OT, and upregulation of intronic RNA expression in magnocellular AVP and OT neurons in response to treatments for which cFos expression and neurosecretion are strongly correlated (hyperosmolality, hemorrhage, vagal activation, suckling following prolonged pup removal), treatments which appear to stimulate cFos expression with little or no neurosecretion (icv and intraparenchymal antiotensin II and neuropeptide Y), and treatments that stimulate release of AVP or OT without cFos expression (suckling following brief pup removal). Studies of parvocellular neurons will continue use the established link between cFos and transmitter release to characterize the functional interrelations among hypothalamic and limbic systems participating in the modulation of food intake. These studies will evaluate the hypothesis that diverse treatments which inhibit food intake activate a common subset of neurons in the brainstem that projects to and is reciprocally innervated by a different subset of neurons with unique connectivity patterns. This will be accomplished by study of the interrelations between neurons that express cFos following treatments that inhibit or increase food intake through a combination of staining for cFos expression, retrograde tracing, and phenotypic charaction of the neurons activated in response to treatments that inhibit food intake (CCK and LiCl administration, hyperosmolality, icv injection of OT, food ingestion), and treatments that stimulate food intake (insulin-induced hypoglycemia, icv administration of neuropeptide Y, food deprivation). Together these studies will both expand the limits and clarify the interpretations of using cFos immunocytochemistry to map functional neuroanatomical circuits.
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