The long term goal of my research program is to understand how social interactions among individuals produce specific changes in the brain. Although it is common to study how the brain controls behavior, understanding how the brain can be influenced by behavior offers uncommon challenges. To discover principles underlying the causal mechanisms, we study reproduction, arguably the most important event in an animal’s life. The brain-pituitary-gonadal axis that controls vertebrate reproduction has been conserved throughout the evolution of vertebrates as evidenced by the fact that the primary signaling molecule, gonadotropin-releasing hormone (GnRH), has had the same size and structure for 500 million years of vertebrate evolution. Understanding how behavior influences this essential physiological axis should reveal fundamental principles about the mechanisms of reproductive control.

We have previously shown that a change in the social status of an individual male causes a reversible change in the size of an identified group of GnRH containing neurons in the preoptic area of the brain. In females, similar changes in cell size occur, but they are controlled by the reproductive state, not the social scene. We have shown that when adult teleost males become socially dominant by acquiring a territory, neurons that contain gonadotropin releasing hormone (GnRH) enlarge significantly. Conversely, losing a territorial fight results in those same cells decreasing in size. These cells are key players in the brain-pituitary-gonadal axis that controls reproduction. Here we propose to discover how the recognition of social opportunity is translated into cell-specific change. Three sets of experiments are proposed to address questions at several levels of analysis.

The first set of experiments examines the molecular mechanisms of social control, based on our demonstration that a change in social status of males produces a change in abundance of GnRH mRNA in the POA neurons (White & Fernald, 1998c). We now propose to understand the mechanisms underlying the social control of GnRH gene expression, including the regulation of GnRH mRNA at the level of primary transcript, processing intermediate or mature mRNA and the regulation of GnRH peptide levels. Although GnRH regulation is expected, there may also be regulation of GnRH receptor expression. In the second set of experiments, we will measure the change in pituitary GnRH receptor mRNA levels and the change in GnRH receptor protein levels in response to changes in social status. We anticipate that social information will influence numerous, interrelated physiological pathways responsible for transducing social information into neuronal change. Based on our discovery that cortisol is an important factor intermediate between behavior and cellular change (Fox et al., 1997), in a third set of experiments, we propose to manipulate cortisol levels to discover whether and how cortisol influences behavior and GnRH abundance.

The results from the proposed experiments should provide new insights into mechanisms through which social encounters influence the brain, expanding our understanding of how social interactions influence cellular and molecular processes necessary for subsequent behavior. Since the brain-pituitary-gonadal axis is common to all vertebrates, these discoveries will have wide application in the analysis of reproduction and its social control.

Model System ⇒