Project description:Here, we investigated the effects of Rhynchophylline (RHY) on the mouse brain spatial transcriptome. More precisely, we injected male and female mice intraperitoneally with either saline (NaCl) or RHY, either at Zeitgeber time (ZT referring to time in hour after light onset) 0 or ZT0 and ZT11. Brains were sampled at ZT4 or ZT14, respectively, and immediately frozen embedded in OCT. Brains were treated and libraries were prepared according to 10x Genomics protocols for Visium Spatial Gene Expression. Sequencing was conducted by Genome Quebec (Montreal, Quebec, Canada). Findings reveal molecular routes by which RHY acts on the brain in a sleep-relevant context. Please cite the original paper when using these data (Ballester Roig et al., Biol Direct, 2023) and see also the submission GSE217058.
Project description:Here, we investigated the effects of Rhynchophylline (RHY) on the mouse brain spatial transcriptome. More precisely, we injected male and female mice intraperitoneally with either saline (NaCl) or RHY, either at Zeitgeber time (ZT referring to time in hour after light onset) 0 or at ZT0 and ZT11. Brains were sampled at ZT4 or ZT14, respectively, and immediately frozen embedded in OCT. Brains were treated and libraries were prepared according to 10x Genomics protocols for Visium Spatial Gene Expression. Sequencing was conducted by Genome Quebec (Montreal, Quebec, Canada). Findings reveal molecular routes by which RHY acts on the brain in a sleep-relevant context. Please cite the original paper when using these data (Ballester Roig et al., Biol Direct, 2023).
Project description:This project explores dietary proteins in human dental calculus through shotgun proteomics. These files are in addition to those accidentally not included in the original publication, Dairying enabled Early Bronze Age Yamnaya steppe expansions . DOI https://doi.org/10.1038/s41586-021-03798-4. Files include raw, mgf, and mzid files from the two Botai individuals: DA092 (Botai 2A), DA089 (CII(3) 30-40), and additional files from Russian sites: DA431, DA431 (Lebyazhinka 5, LEB N-0), Z333 (Khvalynsk 2, KHA2 N-12), and Z444 (Murziha 2, MUR2 N-128) as well as the blanks used in the experiments. It also inlcludes the corresponding files for DA436, as in the previous upload an under-injected sample was included as the MDF.
Project description:Homeostatic scaling is a global form of synaptic plasticity used by neurons to adjust overall synaptic weight and maintain neuronal firing rates while protecting information coding. While homeostatic scaling has been demonstrated in vitro, a clear physiological function of this plasticity type has not been defined. Sleep is an essential process that modifies synapses to support cognitive functions such as learning and memory. Evidence suggests that information coding during wake drives synapse strengthening which is offset by weakening of synapses during sleep .Here we use biochemical fractionation, proteomics and in vivo two-photon imaging to characterize wide-spread changes in synapse composition in mice through the wake/sleep cycle. We find that during the sleep phase, synapses are weakened through dephosphorylation and removal of synaptic AMPA-type glutamate receptors (AMPARs) driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors (mGluR1/5), consistent with known mechanisms of homeostatic scaling-down in vitro. Further, we find that these changes are important in the consolidation of contextual memories. While Homer1a gene expression is driven by neuronal activity during wake, Homer1a protein targeting to synapses serves as an integrator of arousal and sleep need through signaling by the wake-promoting neuromodulator noradrenaline (NA) and sleep-promoting modulator adenosine. During sleep or periods of increased sleep need Homer1a enters synapses where it remodels mGluR1/5 signaling complexes to promote AMPAR removal. Thus, we have characterized widespread changes occurring at synapses through the wake/sleep cycle and demonstrated that known mechanisms of homeostatic scaling-down previously demonstrated only in vitro are active in the brain during sleep to remodel synapses, contributing to memory consolidation.
Project description:In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) M-NM-8 power during wakefulness and M-NM-4 power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in M-NM-4 power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. Mice recievied 12 hours of sleep restriction during the 12 hours of light in the light-dark cycle Boxhill represents Per35/5 mice and Coach represents Per34/4 mice. A total of 48 samples comprising 24 mice
Project description:In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in δ power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.