REM Sleep and Memory

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ABSTRACT The importance of sleep in the memory consolidation process is well accepted and well studied in males. We have generated a good understanding of how neural activity patterns during specific stages of sleep facilitate strengthening, weakening, and reorganization of memory networks. We and others have found that, rapid eye movement (REM) sleep duration and the strength of the theta rhythm, the featured pattern of electrical activity common in REM sleep, contributes to memory processing. One of the important regulators of REM sleep for memory consolidation is the nucleus locus coeruleus in the brainstem which falls silent and thereby allows the depotentiation of synapses necessary for reversal learning. Although the presence of norepinephrine during waking encourages strengthening of synapses, its presence in REM sleep may be maladaptive in the case where new information must be integrated into an old memory schema. Work in our lab has identified the important role of locus coeruleus silence during REM sleep for proper reversal learning. Other features of sleep are also important in learning. However it is entirely unknown whether the locus coeruleus also falls silent in REM sleep in females. Estrogen receptors are found on the locus coeruleus, providing a set-limit function on reactivity to stressful stimuli. Cycling gonadal hormones (like estrogen) also seem to affect sleep quality in humans. We seek to investigate how sleep and locus coeruleus activity is modified across the estrus cycle in females, and see how changes in these parameters might influence mechanisms of memory consolidation in sleep, using a fear conditioning, extinction, and extinction recall learning paradigm dependent on hippocampal learning and on sleep consolidation. Given that females are more vulnerable to anxiety disorders, we want to determine if inappropriate LC activity during sleep, particularly during low hormone phases, contributes to fear memory consolidation deficits. The fundamental discoveries made in this grant period should provide groundbreaking knowledge in how the estrous cycle alters sleep features and brain areas that are important in learning so that future advances can be made in addressing mental health in females.