Neural mechanisms of REM sleep: circadian influence.

Sleep is a fundamental biological process identified in virtually in all species of animals. Of various stages of sleep, rapid eye movement (REM) sleep is unique in that the brain is active but the body is totally asleep except for rapid eye movements. REM sleep peaks towards the end of the sleep period, and this daily rhythm is known to be driven internally by the circadian (~24 hours) clock housed in the suprachiasmatic nucleus (SCN) of the brain in mammals. We have recently shown that polysialylated neural cell adhesion molecule (PSA NCAM), a molecule that promotes cell-to-cell interaction, plays a role in the diurnal pattern of REM sleep in rats. Specifically, a compound that removes PSA pharmacologically abolished the normal increase in REM sleep in late sleep phase. However, the route of administration was such that it would have affected the entire brain. The SCN, in fact, contains high amounts of PSA NCAM. As a next step, therefore, we will remove PSA NCAM selectively from the SCN and observe effects on REM sleep patterns. Sleep researchers have long thought that REM sleep is regulated by the interaction between REM-on and REM-off neurons in the lower part of the brain. Although the SCN clock presumably influences this on-off switch, there are no direct anatomical connections. We previously identified indirect anatomical connections of the SCN with wake and NREM sleep nuclei. We will use a similar anatomical approach to identify any indirect pathways from the SCN to REM-on and REM-off neurons. The SCN is thought to promote sleep and wake at different times of day (or night), and distinct SCN neurons are thought to influence different physiological functions. Using timed c-Fos (a neuronal activation marker), we will test the hypothesis that SCN neurons that promote REM sleep are different from those that promote wake in their location and projections. These three complementary studies using behavioural, anatomical and neurophysiological techniques will shed light on how the mammalian circadian clock controls the timing of REM sleep to achieve maximal adaptability to the periodic environment.