Our data showed that cardiovascular risk factors were strongly related to carotid atherosclerosis and that the proportion of severe carotid atherosclerosis with >50% stenosis was not low and was almost equal to that reported in developed western countries.

Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area.Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep.

Previous studies have demonstrated that macromolecular synthesis in the brain is modulated in association with the occurrence of sleep and wakefulness. Similarly, the spectral composition of electroencephalographic activity that occurs during sleep is dependent on the duration of prior wakefulness. Since this homeostatic relationship between wake and sleep is highly conserved across mammalian species, genes that are truly involved in the electroencephalographic response to sleep deprivation (SD) might be expected to be conserved across mammalian species. Therefore, in the rat cerebral cortex, we have studied the effects of SD on the expression of immediate early gene (IEG) and heat shock protein (HSP) mRNAs previously shown to be upregulated in the mouse brain in SD and in recovery sleep (RS) after SD. We find that the molecular response to SD and RS in the brain is highly conserved between these two mammalian species, at least in terms of expression of IEG and HSP family members. Using Affymetrix Neurobiology U34 GeneChips ® , we also screened the rat cerebral cortex, basal forebrain, and hypothalamus for other genes whose expression may be modulated by SD or RS. We find that the response of the basal forebrain to SD is more similar to that of the cerebral cortex than to the hypothalamus. Together, these results suggest that sleep-dependent changes in gene expression in the cerebral cortex are similar across rodent species and therefore may underlie sleep historydependent changes in sleep electroencephalographic activity. KeywordsTaqman analysis; sleep deprivation; immediate early genes; basal forebrain; cerebral cortex; hypothalamus HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptSleep is a homeostatic process in that the time spent asleep and the continuity of sleep states are directly related to the duration of prior wakefulness. Although sleep duration and the time spent in each of its stages are parameters commonly measured in sleep studies, sleep also has an intensity dimension, measurable by slow wave activity (SWA) in the electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep. The amplitude of EEG SWA is directly proportional to the duration of prior wake and consequently has been proposed as a marker for the homeostatic regulation of sleep in mammals (Borbely and Achermann, 2000). Accordingly, sleep need, measurable as EEG SWA once sleep is initiated, is thought to accrue during wakefulness. Conversely, the decline of EEG SWA amplitude across a sleep bout is thought to reflect the diminution of the sleep-dependent "Process S" that reflects recovery from prior waking activities.The temporal dynamics of the sleep-dependent discharge of sleep need (reflected in the decay of the sleep-dependent Process S) is conserved among genetically distinct rodent strains (Franken et al., 2001). The conserved nature of Process S supports the concept that EEG SWA may be an electrophysiological marker of restorative neurochemical processes that occur during...

The neural mechanisms underlying memory regulation during sleep are not yet fully understood. We found that melanin concentrating hormone–producing neurons (MCH neurons) in the hypothalamus actively contribute to forgetting in rapid eye movement (REM) sleep. Hypothalamic MCH neurons densely innervated the dorsal hippocampus. Activation or inhibition of MCH neurons impaired or improved hippocampus-dependent memory, respectively. Activation of MCH nerve terminals in vitro reduced firing of hippocampal pyramidal neurons by increasing inhibitory inputs. Wake- and REM sleep–active MCH neurons were distinct populations that were randomly distributed in the hypothalamus. REM sleep state–dependent inhibition of MCH neurons impaired hippocampus-dependent memory without affecting sleep architecture or quality. REM sleep–active MCH neurons in the hypothalamus are thus involved in active forgetting in the hippocampus.

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Background: The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2 -/-) lack circadian rhythms. We studied sleep in cry1,2 -/-mice under baseline conditions as well as under conditions of constant darkness and enforced wakefulness to determine whether cryptochromes influence sleep regulatory processes.

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