This proposal concerns interrelationships among steroid hormones and catecholamine neurotransmitters in relation to sexually dimorphic brain structures mediating the activation of a naturally occurring motivated behavior, male sexual behavior. In Japanese quail, the animal model system investigated here, testosterone is able to activate both motivational and performance components of male-typical reproductive behaviors in adult males but does not activate all aspects of the behavior in adult females. The endocrine mechanisms occurring during embryonic development that control the differentiation of this sex difference in response to testosterone are understood. This hormonal activation in adulthood requires the metabolism of testosterone to 17beta estradiol by the enzyme aromatase in the preoptic medial nucleus, a brain area that is larger in volume in males than in females. Previous work has established that estradiol acts on behavior both in a slow manner (hours to days) as well as in a fast manner (seconds to minutes) and aromatase is similarly regulated in this bimodal fashion. In the current application 14 experiments organized into 5 aims are proposed.
Aim I concerns male/female differences in the neural circuit controlling male-typical behaviors that might explain the remarkable sex difference in the ability of testosterone to activate behavior. A previously identified functional topography in the preoptic medial nucleus related to the control of motivational and performance components of male-typical behavior will be studied in both males and females and a comparison of the mechanisms controlling these two aspects of the behavior will allow us to identify neuroendocrine mechanisms specific to motivational control.
In Aim II, immediate early gene methods will be utilized to functionally analyze the sexually dimorphic circuit regulating this male-typical motivated behavior, identify the causes of the immediate early gene induction and assess its function.
In aim III, topographic variation in ascending catecholamine projections to the preoptic medial nucleus and gene expression in these cell groups, that have been previously implicated in the control of motivated behaviors, will be assessed in relation to behavioral production.
Aim I V concerns the mechanisms regulating rapid changes in the activity of aromatase in vivo and Aim V involves studies of the receptor systems and brain areas mediating the rapid effects of estrogen on behavior. These studies on the neuroendocrine control of sexual motivation provide an assay for understanding the effects of steroid hormones on sex and gender differences in the control of motivated behaviors. Such studies are essential for the development of a scientific underpinning for treatments designed to address behavioral pathologies connected to mental health. Investigations of sex differences in steroid hormone activation of motivated behaviors can also provide insight into the etiology of sexually differentiated and/or hormone- regulated psychiatric diseases. A wide variety of neurological and psychiatric syndromes, likely related to imbalances in monoaminergic neurotransmission, are more common in males, or are more common in females, suggesting that sex differences in the secretion and action of sex steroid hormones may be involved in the development and/or maintenance of these syndromes. The study of steroid hormone-neurotransmitter interactions can provide insight into the etiology of sexually differentiated or steroid-dependent diseases. Alteration in steroid hormone functioning may have major consequences on the control of affective and sexual motivated behaviors in humans and these effects are in all probability mediated by the steroid-induced alterations of neurotransmission.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Simmons, Janine M
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Johns Hopkins University
Schools of Arts and Sciences
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Cornil, Charlotte A (2018) On the role of brain aromatase in females: why are estrogens produced locally when they are available systemically? J Comp Physiol A Neuroethol Sens Neural Behav Physiol 204:31-49
Cornil, Charlotte A; Ball, Gregory F; Balthazart, Jacques (2018) Differential control of appetitive and consummatory sexual behavior by neuroestrogens in male quail. Horm Behav :
Cornil, Charlotte Anne; de Bournonville, Catherine (2018) Dual action of neuro-estrogens in the regulation of male sexual behavior. Gen Comp Endocrinol 256:57-62
Balthazart, Jacques; Choleris, Elena; Remage-Healey, Luke (2018) Steroids and the brain: 50years of research, conceptual shifts and the ascent of non-classical and membrane-initiated actions. Horm Behav 99:1-8
Balthazart, Jacques (2017) Steroid metabolism in the brain: From bird watching to molecular biology, a personal journey. Horm Behav 93:137-150
Balthazart, Jacques; Court, Lucas (2017) Human Sexual Orientation: The Importance of Evidentiary Convergence. Arch Sex Behav 46:1595-1600
Ball, Gregory F (2017) Mechanistic target of rapamycin (mTOR): A mediator of social development. Proc Natl Acad Sci U S A 114:9240-9242
de Bournonville, Catherine; Smolders, Ilse; Van Eeckhaut, Ann et al. (2017) Glutamate released in the preoptic area during sexual behavior controls local estrogen synthesis in male quail. Psychoneuroendocrinology 79:49-58
Iyilikci, Onur; Balthazart, Jacques; Ball, Gregory F (2016) Medial Preoptic Regulation of the Ventral Tegmental Area Related to the Control of Sociosexual Behaviors. eNeuro 3:
Rudolph, Lauren M; Cornil, Charlotte A; Mittelman-Smith, Melinda A et al. (2016) Actions of Steroids: New Neurotransmitters. J Neurosci 36:11449-11458

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