Brain Mechanisms of Reproductive Behavior

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Great progress has been made in the analysis of hormonal, neural and genetic mechanisms underlying a simple sex behavior, lordosis. Now, it would be exciting to understand the flow of behaviors leading up to mating. Also, to explore the behavioral dispositions underlying these proceptive behaviors by the female. We have discovered active approach and pacing behaviors, previously thought to be absent, in female mice. New experiments with mice will allow for 'state of the art' genetic elucidation. (Aim I.): To finish carefully characterizing these locomotor, approach, proceptive and pacing behaviors. Included are quantitative analyses in seminatural environments which encourage a full range of social behaviors by the female, in their natural form. We have already discovered Direct Approaches, Head Turns, Hop-and-Stops, and Dart/Return Pacing responses. This is almost finished and will not take long. (Aim I1.): We will determine their hormonal facilitation. For the first time in mice, the relative importance of estrogens (E), progestins (P) and their combination will be explored. New data comparing the roles of P and the gene for PRs in small shoebox cages compared to a seminatural environment already show us the importance of context in discerning hormone/gene/behavior causal relations. (Aim III): We will discover their CNS sites of hormone action and genetic influences. For the genetics, primarily, a novel antisense technology will be used. Both hormonal experiments and antisense DNA experiments will include the use of a new 'microsphere' delivery system for hormones and for antisense DNA reagents. The antisense and microsphere techniques, well documented elsewhere, can be applied for the first time to the mouse CNS. Using female mice allows us to apply novel genetic tools. Analyzing the entire sequence of behaviors preceding lordosis, we can address scientifically exciting questions about reproductive behaviors which are not simple and which are biologically important. These behaviors bring together, at the right time, conspecifics who are competent to reproduce. Further, increasing attention to broader, hormone-dependent behavioral dispositions brings us one step closer to issues important for women's health.