The Specific Aim of this research proposal is to add contemporary neuroanatomical and neurophysiological techniques to the methodological armamentarium of the applicant's laboratory in order to further examine the neurobiological basis underlying the onset of puberty in the rhesus monkey, a representative higher primate. To accomplish this, studies will be initiated in the laboratory of Dr. Theodosis at the University of Bordeaux to address the hypothesis that puberty in primates is triggered by a structural remodelling of the hypothalamic neuronal network that provides the hypophysiotropic drive to the pituitary-gonadal axis. The laboratory in Bordeaux was selected for this purpose because it is recognized for its pioneering work on plasticity in another neuroendocrine system; namely, the hypothalamic oxytocinergic- neurohypophysial unit. Three specific questions will be addressed: 1) is the pubertal reamplification of pulsatile GnRH release produced as a result of structural reorganization at the level of the median eminence?; 2) does the median eminence represent a major site of synchronization in the control of pulsatile GnRH release?: 3) does PSA-NCAM play a role in the pubertal reactivation of pulsatile GnRH secretion? Quantitative electron microscopy, immunocytochemistry, con focal microscopy, and optical recording with Ca2+ fluorescent sensitive probes will be employed. Additionally, the potential to apply electrophysiological techniques and molecular biological approaches, such as antisense mRNA technology and gene transfer with viral vectors, to the problem will also he considered. It is hoped that as a result of the work in Bordeaux, the applicant will be better equipped to continue to examine the mystery of puberty: a fundamental problem in
