The long term goal of the experiments proposed here is to understand the mechanisms through which social interactions influence the nervous system. Specifically, how do social encounters between individuals produce cell specific changes in the brain? This will be investigated by studying the well defined social system of a teleost fish and manipulating its social and reproductive states under controlled laboratory conditions that mimic their natural environment. The forebrain magnocellular neurons which contain gonadotropin-releasing hormone (GnRH) will be analyzed with newly developed cellular and molecular probes as well as new techniques. In this system we have shown that when males win a territorial encounter, neurons containing GnRH enlarge by ca. 8-fold in volume and when males lose such an encounter, these same cells shrink. This system offers numerous advantages for the analysis of the cellular consequences of social behavior. Forebrain GnRH neurons comprise a phylogenetically ancient system that plays a central role in modulation pituitary control of reproduction through gonadal control in all vertebrates. The remarkable conservation of the form and size of GnRH during 500 myr of vertebrate evolution allows analysis of mechanisms conserved among vertebrates in a system particularly amenable to experimentation because it allows the use of naturally occurring behavior in the study of cellular and molecular events. The reproductive control system is complicated in mammals because of the superimposition of neocortical functions, but basal forebrain control can be readily studied in teleost fish that do not have these structures. Experiments are planned to address four key questions about the cellular consequences of behavioral action: What molecular mechanism are responsible for changes in the control of GnM abundance? Does social change regulate GnRH receptors at the molecular level? What are the mechanisms responsible for the transduction of social information into cellular change? Control of GnRH-containing neurons has important consequences for all vertebrates because they directly modulate pituitary function. For example, these cells are implicated in growth or maturation related diseases such as hypogonadism and juvenilized physiognomy. Understanding how production of GnRH is socially regulated will enhance our ability to treat malfunctions of this important brain system.
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