Sleep occupies one-third of our adult lives and yet we still do not know its function. As surprising as this may seem, consider that sleep occupies over two-thirds of the daily lives of infants and yet the vast majority of sleep research concerns its phenomenology and function in adults. Moreover, controversy still surrounds the nature of infant sleep, its relationship to adult sleep, and its neural substrates. A guiding theme of this proposal is that a satisfactory explanation of sleep development, and ultimately sleep's function, will emerge most readily from focused, mechanistic investigations of individual sleep components and their associated neural circuitry during infancy. Two components of active (REM) sleep are nuchal muscle atonia and myoclonic twitching, which together help to define a coherent sleep state in infant rats. It was found recently that 2-day-old (P2) rats cycle rapidly between sleep and wakefulness and that these cycles lengthen significantly over the first postnatal week. Building on this finding, the modulation of sleep cyclicity by circadian factors, moderate and extreme cold exposure, and food deprivation will be investigated. In addition, a novel method for depriving infants of sleep is proposed. These experiments are essential to describe fully the factors that modulate normal sleep in the developing infant and to evaluate the infant's ability to regulate sleep homeostatically. Next, neurophysiological and selective lesioning techniques will be used to explore the neural mechanisms that contribute to sleep cycle development between P2 and P8, as well as a second transition that occurs between P10 and P15. This second transition covers a period characterized by the development of slow-wave sleep (SWS), the second major category of sleep. Specific hypotheses concerning the neural mechanisms that modulate these transitions will be tested in unanesthetized and unrestrained infant rats using multisite electrodes implanted into mesopontine, thalamic, hypothalamic, and forebrain structures implicated in the control of sleep in adults. All together, the experiments proposed here address basic issues in sleep development that have not been systematically explored. It is expected that a more thorough understanding of the development of sleep will provide useful insights into the causes and treatment of sleep and developmental disorders in preterm and full-term infants, as well as adults.
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