A dynamic deep sleep stage in Drosophila.

How might one determine whether simple animals such as flies sleep in stages? Sleep in mammals is a dynamic process involving different stages of sleep intensity, and these are typically associated with measurable changes in brain activity (Blake and Gerard, 1937; Rechtschaffen and Kales, 1968; Webb and Agnew, 1971). Evidence for different sleep stages in invertebrates remains elusive, even though it has been well established that many invertebrate species require sleep (Campbell and Tobler, 1984; Hendricks et al., 2000; Shaw et al., 2000; Sauer et al., 2003). Here we used electrophysiology and arousal-testing paradigms to show that the fruit fly, Drosophila melanogaster, transitions between deeper and lighter sleep within extended bouts of inactivity, with deeper sleep intensities after ∼15 and ∼30 min of inactivity. As in mammals, the timing and intensity of these dynamic sleep processes in flies is homeostatically regulated and modulated by behavioral experience. Two molecules linked to synaptic plasticity regulate the intensity of the first deep sleep stage. Optogenetic upregulation of cyclic adenosine monophosphate during the day increases sleep intensity at night, whereas loss of function of a molecule involved in synaptic pruning, the fragile-X mental retardation protein, increases sleep intensity during the day. Our results show that sleep is not homogenous in insects, and suggest that waking behavior and the associated synaptic plasticity mechanisms determine the timing and intensity of deep sleep stages in Drosophila.

Oscillatory brain activity in spontaneous and induced sleep stages in flies.

Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABAA agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.

Will testing for apolipoprotein E assist in tailoring dementia risk reduction? A review.

This paper aims to systematically review the influence of apolipoprotein E (ApoE) on the effects of potentially modifiable mid and late life risk factors for dementia. Scopus, Medline, PubMed, PsycINFO, and HuGE databases were searched up to November 2008. Two independent reviewers selected 94 articles from 13,122 results. Results suggest the deleterious effect of current smoking is limited only to persons without ApoE epsilon 4 (4 out of 4 studies), ApoE epsilon 4 increases the risk of dementia associated with greater fat consumption, particularly saturated fats (3 out of 4 studies), and increases the protective effect against dementia associated with HRT use (3 out of 5 with one of the non-significant studies suggesting a trend). There was evidence that ApoE does not modify the risk of dementia associated with measures of, and treatments for CVD, other dietary factors, and estradiol levels. There was inconsistent or contradictory evidence for other environmental factors reviewed. There is insufficient evidence for the recommendation of ApoE testing to assist with tailoring risk reduction recommendations for dementia.