Lordosis, as part of female rat reproduction, provides a unique opportunity to relate molecular changes to behavior, because of the great amount of previous work on its hormonal mechanisms, sensory and motor components, and circuitry. Several neurochemical products have been implicated in lordosis control. We have selected strong candidates for relating molecular synthesis of specific transmitters and peptides to lordosis. We suspect that different gene expression systems may play different roles in the neuro-endocrine control of reproduction, and need to explore how each is related to lordosis. Thus, we will use in situ hybridization and single unit activity to compare molecular and electrophysiological results to lordosis measures. In turn, to tie these cellular results to behavior, where possible, we will manipulate molecular events to cause lordosis changes. Experiment set I. deals with 2 transmitter systems involved in lordosis in the rat hypothalamus: alpha-1 adrenergic and muscarinic. For each we will study the ability of E and P to alter messenger RNA levels for the appropriate receptor, and will use in vitro recordings of single unit activity to study E and P effects on hypothalamic neuronal responses to the appropriate agonists. Results with these two cellular approaches will be related to the effects of alpha-1 adrenergic agonists and muscarinic agonists on lordosis. Where possible, situational constraints on the actions of a given system will be hypothesized and tested. Experiment set II. deals with 3 neuropeptide systems involved in lordosis. LHRH gene expression will be studied under E and P conditions designed to allow tight correlations with lordosis, and its electrophysiological effects as a neuromodulator will be analyzed. Enkephalin gene expression will be correlated with lordosis performance under selected hormonal conditions. Oxytocin gene expression will be studied as a function of situational constraints which may reveal the nature of oxytocin's contributions to lordosis. Throughout, identification of the neuronal groups studied will be confirmed using combinations of techniques: we will follow electrophysiological and behavioral measurements with histochemical examination of the same tissue, including in situ hybridization and immunocytochemistry. Thus, we will be better able to see how molecular events in particular neuronal groups contribute to the occurrence of lordosis. Overall, the design of this project and the technical history of this lab allow detailed approaches to reductionistic brain mechanisms while maintaining a strict behavioral focus.
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