Pauline Yahr - US grants

The goal of this research is to understand how gonadal steroids act on the brain to modify mammalian social behaviors. It is pursued by focusing on how testosterone (T) activates social behaviors in adult males and affects sexual differentiation. In each case, parallel analyses examine the effects of T on sexually dimorphic cell groups in the preoptic area (POA) of the hypothalamus and on masculine behaviors involved in reproduction and communication. The research will capitalize on the fact that the sexually dimorphic area (SDA) of the gerbil POA has been implicated in the hormonal control of male sexual behavior and scent marking, a form of olfactory communication. The SDA is a set of hormone- accumulating cell groups that responds to T morphologically and histochemically in adulthood. At least one subdivision of the SDA, the SDA pars compacta (SDApc) also sexually differentiates under the control of T during early development. While structural sex differences have been identified in the POA of at least nine species, including humans, evidence linking the SDA to hormonal control of masculine social behaviors is stronger than in any other species. Thus it is the best model available for attempting to identify cellular markers of T action and the neural pathways involved in these behaviors. During the period of requested support, this model will be developed further by (1) determining if cell-body lesions of the SDA disrupt mating and marking as electrolytic lesions do, and if the deficits are related to damage to specific subdivisions; (2) determining if it is easier to elicit marking or mating with hormone implants in the SDA than in adjacent areas, and if the effects vary for different subdivisions; (3) studying the distribution of muscarinic receptors in the SDA and their relationship to the facilitation of scent marking by muscarinic antagonists; (4) determining which afferents and efferents are important for mating or marking and if any mediated the effects of T on the SDA; (5) determining if SDA cells directly link the pertinent afferents; (6) determining if the pertinent input, output or intervening SDA cells accumulate T or its metabolites; (7) attempting to identify the transmitters/modulators of the behaviorally important pathways; (8) studying the effects of pudental nerve cuts on the SDApc; and (9) continuing research on sexual differentiation of the SDA and SDApc. Processes affecting the development and expression of sexual and communication behaviors clearly affect mental health.

DESCRIPTION (Adapted from applicant's abstract): The long-term goal of this research is to understand how testosterone (T) acts on the brain to modify male social behaviors. During the period of requested support, the focus will be on the activation of mating in adult males to capitalize on the identification of cell groups in the gerbil medial preoptic area, and related pathways, that are essential for this behavior. The critical cell groups are the two major parts of the sexually dimorphic area (SDA). The pathways are a projection from the SDA to the retrorubral field (RRF) and a reciprocal connection of the SDA with the medial bed nucleus of the stria terminalis (BSTm). To learn more about the circuitry for male sex behavior, four aims of this research are 1) to test whether SDA efferents to the RRF use gamma-amino-butyric acid (GABA) as their transmitter, 2) to test whether the pedunculopontine tegmental nucleus contributes to any effects attributed to the RRF, 3) to determine if the RRF and caudal BSTm affect mating as parts of a common pathway and 4) to test the hypothesis that the medial part of the medial preoptic nucleus of rats is analogous to the gerbil medial SDA. Another cell group, the SDA parts compacta (SDApc), which is seen almost exclusively in males in adulthood, is not essential for male sex behavior. Aim 5 is to test whether it affects other aspects of reproduction. SDA cell groups also show specific patterns of activation during mating as assessed by c-Fos immunocytochemistry. The medial SDA responds when males enter the sexual context and when they ejaculate. A thalamic nucleus connected to the mSDA shows the same pattern. Part of the posterodorsal medial amygdala (MeApd), which is connected to the mSDA, and the posterodorsal preoptic nucleus, which is near the SDA, respond only with ejaculation. The remaining aims of the research are 6) to test whether either the PdPN or MeApd is causally related to ejaculation (behavior or seminal emission), 7) to assess the relationships among the four cell groups activated with ejaculation and 8) to determine if the MeApd cells involved contain any of the peptides that are dimorphic or T sensitive in the MeApd of other species. The expression of sex behavior can clearly affect both the mental and physical health of men and their partners.