Over the past 20 years, sex differences in the central nervous system have moved from being a subject of speculation to being a focus of intense research and widespread interest. This is because the study of sex differences enhances our understanding of the nervous system in at least two different ways. First, detailed examination of sex differences in a neural circuit of a known behavioral or physiological function may provide insights regarding those aspects of the neural circuit that are critically involved in the display of the function under question. Secondly, sexual differentiation is a fundamental process of development. Thus, knowledge of the mechanisms underlying sex differences may lead to deeper insights into the general processes involved in differentiation specialization of nerve cells and their pattern of connectivity. Dr. Newton has identified a neuromuscular system that can be used as model to examine questions that may lead to a better understanding of both function and development. The cremaster nucleus is a group of motoneurons located in the ventral gray horn of the lumbar spinal cord that project through only one nerve to innervate only one muscle. This nucleus is sexually dimorphic and controls exclusively masculine functions related to testicular physiology. Using state-of-the-art anatomical methodology, Dr. Newton will tease apart the hormonally and non- hormonally mediated events in the development of this system. He will examine how these cremaster motoneurons normally develop and then determine how they are altered by changing the size of the muscle that they innervate and/or by changing the hormonal milieu. The results will provide new insights into how spinal cord neurons respond when their environment is altered. Besides leading to significant advances in concepts regarding developmental interactions between motoneurons, their afferents, their target muscles and control by gonadal hormones, these studies may provide information on which hormonal conditions are best for neuron survival when the muscles which neurons innervate are damaged or if the spinal cord itself is damaged.