Homer1a is a core brain molecular correlate of sleep loss.

Center for Integrative Genomics and Lausanne DNA Array Facility, University of Lausanne, Génopode, CH-1015 Lausanne, Switzerland.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2008; 104(50):20090-5. DOI: 10.1073/pnas.0710131104
Source: PubMed

ABSTRACT Sleep is regulated by a homeostatic process that determines its need and by a circadian process that determines its timing. By using sleep deprivation and transcriptome profiling in inbred mouse strains, we show that genetic background affects susceptibility to sleep loss at the transcriptional level in a tissue-dependent manner. In the brain, Homer1a expression best reflects the response to sleep loss. Time-course gene expression analysis suggests that 2,032 brain transcripts are under circadian control. However, only 391 remain rhythmic when mice are sleep-deprived at four time points around the clock, suggesting that most diurnal changes in gene transcription are, in fact, sleep-wake-dependent. By generating a transgenic mouse line, we show that in Homer1-expressing cells specifically, apart from Homer1a, three other activity-induced genes (Ptgs2, Jph3, and Nptx2) are overexpressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The energy allocation (EA) model defines behavioral strategies that optimize the temporal utilization of energy to maximize reproductive success. This model proposes that all species of the animal kingdom share a universal sleep function that shunts waking energy utilization toward sleep-dependent biological investment. For endotherms, REM sleep evolved to enhance energy appropriation for somatic and CNS-related processes by eliminating thermoregulatory defenses and skeletal muscle tone. Alternating REM with NREM sleep conserves energy by decreasing the need for core body temperature defense. Three EA phenotypes are proposed: sleep-wake cycling, torpor, and continuous (or predominant) wakefulness. Each phenotype carries inherent costs and benefits. Sleep-wake cycling downregulates specific biological processes in waking and upregulates them in sleep, thereby decreasing energy demands imposed by wakefulness, reducing cellular infrastructure requirements, and resulting in overall energy conservation. Torpor achieves the greatest energy savings, but critical biological operations are compromised. Continuous wakefulness maximizes niche exploitation, but endures the greatest energy demands. The EA model advances a new construct for understanding sleep-wake organization in ontogenetic and phylogenetic domains.
    Neuroscience & Biobehavioral Reviews 11/2014; · 10.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transcriptomic studies have revealed that the brains of sleeping and awake animals differ significantly at the molecular level, with hundreds of brain transcripts changing their expression across behavioral states. However, it was unclear how sleep affects specific cell types, such as oligodendrocytes, which make myelin in the healthy brain and in response to injury. In this review, I summarize the recent findings showing that several genes expressed at higher levels during sleep are involved in the synthesis/maintenance of all membranes and of myelin in particular. In addition, I will discuss the effect of sleep and wake on oligodendrocyte precursor cells (OPCs), providing a working hypothesis on the function of REM sleep and acetylcholine in OPC proliferation.
    Current Sleep Medicine Reports. 01/2015;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The epilepsies are a heterogeneous group of neurological diseases defined by the occurrence of unprovoked seizures which, in many cases, are correlated with diurnal rhythms. In order to gain insight into the biological mechanisms controlling this phenomenon, we characterized time-of-day effects on electrical seizure threshold in mice. Male C57BL/6J wild-type mice were maintained on a 14/10 h light/dark cycle, from birth until 6 weeks of age for seizure testing. Seizure thresholds were measured using a step-wise paradigm involving a single daily electrical stimulus. Results showed that the current required to elicit both generalized and maximal seizures was significantly higher in mice tested during the dark phase of the diurnal cycle compared to mice tested during the light phase. This rhythm was absent in BMAL1 knockout (KO) mice. BMAL1 KO also exhibited significantly reduced seizure thresholds at all times tested, compared to C57BL/6J mice. Results document a significant influence of time-of-day on electrical seizure threshold in mice and suggest that this effect is under the control of genes that are known to regulate circadian behaviors. Furthermore, low seizure thresholds in BMAL1 KO mice suggest that BMAL1 itself is directly involved in controlling neuronal excitability.
    Frontiers in Systems Neuroscience 06/2014; 8:121.

Full-text (2 Sources)

Available from
May 22, 2014