Notch Signaling: A Role in Sleep and Stress

Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Current biology: CB (Impact Factor: 9.57). 05/2011; 21(10):R397-8. DOI: 10.1016/j.cub.2011.04.014
Source: PubMed


The molecular pathways regulating sleep remain poorly understood. Studies in this issue demonstrate a role for Notch signaling in sleep regulation as well as stress response in both Caenorhabditis elegans and Drosophila.

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    • "Insects are known to go through rest phases that resemble key features of sleep [Drosophila (Hendricks et al., 2000; Shaw et al., 2000); honeybee (Kaiser, 1988)]. In Drosophila, the genes and signaling cascades that control sleep are already well understood (Sehgal and Mignot, 2011), and some of these regulatory systems can be related to synaptic plasticity and memory consolidation (Foltenyi et al., 2007; Bushey et al., 2011; Seugnet et al., 2011; Wu and Raizen, 2011). The neural networks involved in these cellular processes highlight the role of the mushroom body (Joiner et al., 2006; Guo et al., 2011) and an identified protocerebral cell group, the octopamine-containing neurons in the pars intercerebralis (Crocker et al., 2010), possibly also involved in synaptic plasticity and memory consolidation. "
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    ABSTRACT: Sleep is known to support memory consolidation in animals, including humans. Here we ask whether consolidation of novel navigation memory in honeybees depends on sleep. Foragers were exposed to a forced navigation task in which they learned to home more efficiently from an unexpected release site by acquiring navigational memory during the successful homing flight. This task was quantified using harmonic radar tracking and applied to bees that were equipped with a radio frequency identification device (RFID). The RFID was used to record their outbound and inbound flights and continuously monitor their behavior inside the colony, including their rest during the day and sleep at night. Bees marked with the RFID behaved normally inside and outside the hive. Bees slept longer during the night following forced navigation tasks, but foraging flights of different lengths did not lead to different rest times during the day or total sleep time during the night. Sleep deprivation before the forced navigation task did not alter learning and memory acquired during the task. However, sleep deprivation during the night after forced navigation learning reduced the probability of returning successfully to the hive from the same release site. It is concluded that consolidation of novel navigation memory is facilitated by night sleep in bees.
    Journal of Experimental Biology 11/2012; 215(Pt 22):3981-8. DOI:10.1242/jeb.075499 · 2.90 Impact Factor
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    ABSTRACT: Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.
    Physiological Reviews 04/2013; 93(2):681-766. DOI:10.1152/physrev.00032.2012 · 27.32 Impact Factor
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    ABSTRACT: Drosophila Enhancer of split M8, an effector of Notch signaling, is regulated by protein kinase CK2. The phosphatase PP2A is thought to play an opposing (inhibitory) role, but the identity of the regulatory subunit was unknown. The studies described here reveal a role for the PP2A regulatory subunit widerborst (wdb) in three developmental contexts; the bristle, wing and the R8 photoreceptors of the eye. wdb overexpression elicits bristle and wing defects akin to reduced Notch signaling, whereas hypomorphic mutations in this PP2A subunit elicit opposite effects. We have also evaluated wdb functions using mutations in Notch and E(spl) that affect the eye. We find that the eye and R8 defects of the well-known Nspl mutation are enhanced by a hypomorphic allele of wdb, whereas they are strongly rescued by wdb overexpression. Similarly, ectopic wdb rescues the eye and R8 defects of the E(spl)D mutation, which affects the m8 gene. In addition, wdb overexpression also rescues the bristle defects of ectopically expressed M8, or the eye and R8 defects of its CK2 phosphomimetic variant M8-S159D. The latter finding suggests that PP2A may target M8 at highly conserved residues in the vicinity of the CK2 site, whose phosphorylation controls repression of Atonal and the R8 fate. Together, the studies identify PP2A-Wdb as a participant in Notch signaling, and suggest that M8 activity is controlled by phosphorylation and dephosphorylation. The conservation of the phosphorylation sites between Drosophila E(spl) and the HES/HER proteins from mammals, reptiles, amphibians, birds and fish raises the prospect that this mode of regulation is widespread.
    PLoS ONE 07/2014; 9(7):e101884. DOI:10.1371/journal.pone.0101884 · 3.23 Impact Factor
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