Sleep and synaptic homeostasis: structural evidence in Drosophila.

Department of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
Science (Impact Factor: 31.48). 06/2011; 332(6037):1576-81. DOI: 10.1126/science.1202839
Source: PubMed

ABSTRACT The functions of sleep remain elusive, but a strong link exists between sleep need and neuronal plasticity. We tested the hypothesis that plastic processes during wake lead to a net increase in synaptic strength and sleep is necessary for synaptic renormalization. We found that, in three Drosophila neuronal circuits, synapse size or number increases after a few hours of wake and decreases only if flies are allowed to sleep. A richer wake experience resulted in both larger synaptic growth and greater sleep need. Finally, we demonstrate that the gene Fmr1 (fragile X mental retardation 1) plays an important role in sleep-dependent synaptic renormalization.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases.
    Brain Stimulation 04/2015; 3. DOI:10.1016/j.brs.2015.01.404 · 5.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is increasingly evident that astrocytes, once considered primarily a passive support cell type, in fact respond to and regulate neurotransmission to influence information processing and behavior. Although astrocytes are not electrically excitable, they express a variety of receptors that produce calcium responses able to propagate within and between astrocytes. This form of signaling occurs on spatial and temporal scales distinct from those of neuronal activity, potentially allowing astrocytes to locally regulate synaptic and network activity over extended time periods. Perhaps the best studied example of this regulation is the control of sleep homeostasis by astrocytes. Astrocyte-derived adenosine causes an increase in sleep pressure leading to increased slow wave activity and extended recovery sleep. Despite its established importance for the sleep homeostat, however, the roles of astrocytes in other sleep-associated processes are only beginning to be understood.
    03/2015; 1(1):9-19. DOI:10.1007/s40675-014-0005-5
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Emerging data suggest an important relationship between sleep and Alzheimer's disease (AD), but how poor sleep promotes the development of AD remains unclear. Here, using a Drosophila model of AD, we provide evidence suggesting that changes in neuronal excitability underlie the effects of sleep loss on AD pathogenesis. β-amyloid (Aβ) accumulation leads to reduced and fragmented sleep, while chronic sleep deprivation increases Aβ burden. Moreover, enhancing sleep reduces Aβ deposition. Increasing neuronal excitability phenocopies the effects of reducing sleep on Aβ, and decreasing neuronal activity blocks the elevated Aβ accumulation induced by sleep deprivation. At the single neuron level, we find that chronic sleep deprivation, as well as Aβ expression, enhances intrinsic neuronal excitability. Importantly, these data reveal that sleep loss exacerbates Aβ-induced hyperexcitability and suggest that defects in specific K(+) currents underlie the hyperexcitability caused by sleep loss and Aβ expression. Finally, we show that feeding levetiracetam, an anti-epileptic medication, to Aβ-expressing flies suppresses neuronal excitability and significantly prolongs their lifespan. Our findings directly link sleep loss to changes in neuronal excitability and Aβ accumulation and further suggest that neuronal hyperexcitability is an important mediator of Aβ toxicity. Taken together, these data provide a mechanistic framework for a positive feedback loop, whereby sleep loss and neuronal excitation accelerate the accumulation of Aβ, a key pathogenic step in the development of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Current Biology 03/2015; DOI:10.1016/j.cub.2015.01.016 · 9.92 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014