Michael C. Moore, Ph.D. - US grants

A fundamental problem for behavioral neuroscience is to understand physiological control of individual variation in reproductive behavior and aggression. Progress in explaining sexually dimorphic behavior illustrates that this type of problem is most tractable in systems with discontinuous behavior variation. This application proposes to test the generality of the organization-activation model of hormonal control, which has been successfully applied to hormonal control of sexually dimorphic behavior, to situations of similarly discontinuous within-sex behavior variation. The most common example of the latter occurs in species with alternative male reproductive tactics. The hypothesis proposed predicts that the role that hormones play will depend on whether alternative male phenotypes are fixed or plastic. For fixed phenotypes, hormones should play a greater role during development (organization) than during adulthood (activation). The model system chosen, the tree lizard, has a fixed male behavioral polymorphism. Prior to sexual maturity, males permanently develop into one of two phenotypes. One phenotype is highly aggressive and territorial, whereas the other is less aggressive and appears to be nonterritorial and nomadic in nature. This proposal investigates the role of sex and adrenal steroids during early development in influencing the differentiation of these alternative male phenotypes. Specifically, correlational and manipulative endocrine experiments are combined to test the prediction that hormones act in a way analagous to organization by determining the type of hormone, the effective dose, the timing of hormonal treatment and the type of hormone metabolism necessary to effect phenotype differentiation. Together, the studies provide the first description of the role of hormones in within-sex behavioral differentiation, test the generality of the organizational-activational model and provide basic information useful in understanding behavioral variation, both continuous and discontinuous, in all species, including humans.

A fundamental problem for behavioral neuroscience is to understand physiological control of individual variation in reproductive behavior and aggression. Progress in explaining sexually dimorphic behavior illustrates that this type of problem is most tractable in systems with discontinuous behavior variation. This application proposes to test the generality of the organization-activation model of hormonal control, which has been successfully applied to hormonal control of sexually dimorphic behavior, to situations of similarly discontinuous within-sex behavior variation. The most common example of the latter occurs in species with alternative male reproductive tactics. The hypothesis proposed predicts that the role that hormones play will depend on whether alternative male phenotypes are fixed or plastic. For fixed phenotypes, hormones should play a greater role during development (organization) than during adulthood (activation). The model system chosen, the tree lizard, has a fixed male behavioral polymorphism. Prior to sexual maturity, males permanently develop into one of two phenotypes. One phenotype is highly aggressive and territorial, whereas the other is less aggressive and appears to be nonterritorial and nomadic in nature. This proposal investigates the role of sex and adrenal steroids during early development in influencing the differentiation of these alternative male phenotypes. Specifically, correlational and manipulative endocrine experiments are combined to test the prediction that hormones act in a way analagous to organization by determining the type of hormone, the effective dose, the timing of hormonal treatment and the type of hormone metabolism necessary to effect phenotype differentiation. Together, the studies provide the first description of the role of hormones in within-sex behavioral differentiation, test the generality of the organizational-activational model and provide basic information useful in understanding behavioral variation, both continuous and discontinuous, in all species, including humans.

DESCRIPTION (provided by applicant): A significant problem for biomedicine generally and mental health specifically is understanding how individual variation in phenotype is produced. In this proposal we continue our previous approach of attempting to generalize the dominant model of sexual differentiation, the organizational-activational model, to an understanding of the neuroendocrine mechanisms that produce individual variation in aggressive behavior. For these studies we use a nontraditional model, an animal with alternative male phenotypes or morphs. The morphs differ in color and one morph is highly aggressive, while the other is not. This model system is powerful because we can use color to assign individuals to behavioral phenotypes that differ in only one dimension, aggressiveness. In previous funding periods, we learned that differences in behavior between these morphs are organized by early actions of sex steroid hormones in a manner analogous to the organization of sexual phenotype. This result suggests that differences within the sexes may be produced by mechanisms very similar to those that produce differences between the sexes. We propose here to examine this effect more closely and to focus on a more detailed level of the specific mechanisms within the brain. Where do these hormones act in the brain and how does this change during the course of development? What neuroanatomical and neurochemical changes do these hormones produce to bring about the differences in aggressive behavior? How does experience modify the effects of these hormones on these neural substrates? We also propose to test a working hypothesis, the Dual Gate Hypothesis, that is a specific extension of the organizational-activational model and that proposes that the differences in behavior are produced by the early actions of hormones on at least two specific areas of the brain, the medial amygdala and the periventricular nucleus of the hypothalamus.