Our overall aim is to understand in physiological detail the interaction between the circadian clock that measures the daily light cycle and the reproductive system that is regulated by this light cycle. We will approach this goal by first dissociating the two systems from each other and studying them independently. Although light affects both the clock and the reproductive system, potentially its effects may be experimentally confined to one or the other in at least four different ways: 1) by careful choice of the intensity, duration and wavelength of the light signal itself; 2) by the use of general anesthetics that block its effects on one system but not on the other; 3) by manipulaton of neurotransmitters involved in the neural inputs to one system but not the other; and 4) by exploiting genetic lesions that affect the input pathway to one system but not to the other. We propose experiments that will utilize all four of these general stategies. We hope to obtain unambiguous descriptions of some of the properties of the pathways by which light influences each of the two system and some indication of the extent to which the pathways are independent of each other. We view this study as contributing to increased understanding of a much more general and important problem: How is hypothalamic function regulated by the environment and by other brain structures? The effects of light on the circadian/reproductive axis provide a particularly favorable situation in which to define such interactions experimentally because: 1) light, which can be exceptionally well controlled has profound influences on the reproductive system and is the only important environmental input to the circadian system and 2) much of the neural circuitry is known and the behavior that it controls can be measured with unusual precision. Increased understanding of hypothalamic function is central to the amelioration of many human health problems. Although the relevance of an understanding of circadian organization to problem of sleep, jet lag and other aspects of human performance has been appreciated for some time, its interaction with other brain functions has recently been underlined by the finding that circadian malfunction underlies some kinds of serious affective illness.
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