GAD67-GFP knock-in mice have normal sleep-wake patterns and sleep homeostasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen L
PROVIDER: S-EPMC3201775 | biostudies-other | 2010 Feb
REPOSITORIES: biostudies-other
Publications
GAD67-GFP knock-in mice have normal sleep-wake patterns and sleep homeostasis.
Chen Lichao L McKenna James T JT Leonard Michael Z MZ Yanagawa Yuchio Y McCarley Robert W RW Brown Ritchie E RE
Neuroreport 20100201 3
Gamma-aminobutyric acid (GABA) ergic neurons are important for controlling sleep and wakefulness but are difficult to identify, limiting their study. Knock-in mice with GABAergic neurons labeled by expression of green fluorescent protein (GFP) under control of the glutamate decarboxylase 67 (GAD67) promoter are now extensively used in neuroscience. However, it is unknown whether these mice have a normal sleep phenotype. Compared with wild-type control mice, GAD67-GFP knock-in mice had the same a ...[more]
Similar Datasets
Project description:α-Synuclein (aSyn) participates in synaptic vesicle trafficking and synaptic transmission but its misfolding is also strongly implicated in Parkinson's disease (PD) and other neurodegenerative synucleinopathies in which misfolded aSyn accumulates in different regions of the central and peripheral nervous systems. Although increased aSyn expression levels or altered aggregation propensities likely underlie familial PD with SNCA amplification or mutations, the majority of synucleinopathies arise sporadically, indicating that disease can develop under normal levels of wild-type (wt) aSyn. We report here the development and characterization of a mouse line expressing an aSyn-green fluorescence protein (GFP) fusion protein under the control of native Snca regulatory elements. Regional and subcellular localization of the aSyn-GFP fusion protein in brains and peripheral tissues of knock-in (KI) mice are indistinguishable from that of wt littermates. Importantly, similar to wt aSyn, aSyn-GFP disperses from synaptic vesicles on membrane depolarization, indicating that the tag does not alter normal aSyn dynamics at synapses. In addition, intracerebral injection of aSyn pre-formed fibrils into KI mice induced the formation of aSyn-GFP inclusions with a distribution pattern similar to that observed in wt mice, albeit with attenuated kinetics because of the GFP-tag. We anticipate that this new mouse model will facilitate in vitro and in vivo studies requiring in situ detection of endogenous aSyn, thereby providing new insights into aSyn function in health and disease.
| S-EPMC7470929 | biostudies-literature
Project description:Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif) receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT) littermates. Intraperitoneal injection of lipopolysaccharide (LPS) promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.
| S-EPMC5706730 | biostudies-literature
Project description:Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.
| S-EPMC4447375 | biostudies-literature
Project description:Fumarylacetoacetate hydrolase (FAH) is the last enzyme in tyrosine catabolism, and mutations in the FAH gene are associated with hereditary tyrosinemia type I (HT1 or TYRSN1) in humans. In a behavioral screen of N-ethyl-N-nitrosourea mutagenized mice we identified a mutant line which we named "swingshift" (swst, MGI:3611216) with a nonsynonymous point mutation (N68S) in Fah that caused age-dependent disruption of sleep-wake patterns. Mice homozygous for the mutation had an earlier onset of activity (several hours before lights off) and a reduction in total activity and body weight when compared with wild-type or heterozygous mice. Despite abnormal behavioral entrainment to light-dark cycles, there were no differences in the period or phase of the central clock in mutant mice, indicating a defect downstream of the suprachiasmatic nucleus. Interestingly, these behavioral phenotypes became milder as the mice grew older and were completely rescued by the administration of NTBC [2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione], an inhibitor of 4-hydroxyphenylpyruvate dioxygenase, which is upstream of FAH. Mechanistically, the swst mutation had no effect on the enzymatic activity of FAH, but rather promoted the degradation of the mutant protein. This led to reduced FAH protein levels and enzymatic activity in the liver and kidney (but not the brain or fibroblasts) of homozygous mice. In addition, plasma tyrosine-but not methionine, phenylalanine, or succinylacetone-increased in homozygous mice, suggesting that swst mutants provide a model of mild, chronic HT1.
| S-EPMC6825319 | biostudies-literature
Project description:Study objectivesTo compare sleep/wake patterns in children born preterm in Australia vs Canada and determine cultural differences in the relationship between parental perception of sleep and actual sleep behaviors.MethodsAustralian and Canadian children born preterm were recruited from the Caffeine for Apnea of Prematurity trial (n = 188, 5-12 y) and underwent 14 days actigraphy monitoring. Parents completed the National Sleep Foundation 2004 Sleep in America questionnaire. Cross-cultural differences in sleep characteristics assessed by actigraphy and parent-reported questionnaire were examined. Correlational analyses determined the associations between parental perceptions of child sleep need and sleep behavior.ResultsActigraphy showed preterm children obtained, on average, 8 h sleep/night, one hour less than population recommendations for their age. There was no difference in total sleep time (TST) between Australian and Canadian cohorts; however, bed and wake times were earlier in Australian children. Bedtimes and TST varied by 60 minutes from night to night in both cohorts. Parent-reported child TST on the National Sleep Foundation questionnaire was 90 minutes longer than recorded by actigraphy. Both bedtime and TST on weekdays and weekends were related to parental perception of child sleep need in the Australian cohort. Only TST on weekdays was related to parental perception of child sleep need in the Canadian cohort.ConclusionsThis study suggests that short sleep duration and irregular sleep schedules are common in children born preterm. Cultural differences in the association between parental perception of child sleep need and actual sleep behaviors provide important targets for future sleep health education.
| S-EPMC4865558 | biostudies-literature
Project description:Sleep is a fundamental biological rhythm involving the interaction of numerous brain structures and diverse neurotransmitter systems. The primary measures used to define sleep are the electroencephalogram (EEG) and electromyogram (EMG). However, EEG-based methods are often unsuitable for use in high-throughput screens as they are time-intensive and involve invasive surgery. As such, the dissection of sleep mechanisms and the discovery of novel drugs that modulate sleep would benefit greatly from further development of rapid behavioral assays to assess sleep in animal models. Here is described an automated noninvasive approach to evaluate sleep duration, latency, and fragmentation using video tracking of mice in their home cage. This approach provides a high correlation with EEG/EMG measures under both baseline conditions and following administration of pharmacological agents. Moreover, the dose-dependent effects of sedatives, stimulants, and light can be readily detected. This approach is robust yet relatively inexpensive to implement and can be easily incorporated into ongoing screening programs to provide a powerful first-pass screen for assessing sleep and allied behaviors.
| S-EPMC4650254 | biostudies-literature
Project description:Sleep plays a key role in multiple cognitive functions and sleep pattern changes with aging. Human studies revealed that aging decreases sleep efficiency and reduces the total sleep time, the time spent in slow-wave sleep (SWS), and the delta power (1-4 Hz) during sleep; however, some studies of sleep and aging in mice reported opposing results. The aim of our work is to estimate how features of sleep-wake state in mice during aging could correspond to age-dependent changes observed in human. In this study, we investigated the sleep/wake cycle in young (3 months old) and older (12 months old) C57BL/6 mice using local-field potentials (LFPs). We found that older adult mice sleep more than young ones but only during the dark phase of sleep-wake cycle. Sleep fragmentation and sleep during the active phase (dark phase of cycle), homologous to naps, were higher in older mice. Older mice show a higher delta power in frontal cortex, which was accompanied with similar trend for age differences in slow wave density. We also investigated regional specificity of sleep-wake electrographic activities and found that globally posterior regions of the cortex show more rapid eye movement (REM) sleep whereas somatosensory cortex displays more often SWS patterns. Our results indicate that the effects of aging on the sleep-wake activities in mice occur mainly during the dark phase and the electrode location strongly influence the state detection. Despite some differences in sleep-wake cycle during aging between human and mice, some features of mice sleep share similarity with human sleep during aging.
| S-EPMC6769075 | biostudies-literature
Project description:The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in the cytoplasm. Furthermore, we found that the time delay and robustness in the circadian clock are seamlessly generated by delayed and collective phosphorylation of PER molecules, followed by synchronous nuclear entry. These results provide clear mechanistic insight into why circadian and sleep disorders arise in such clinical conditions as metabolic and neurodegenerative diseases and aging, in which the cytoplasm is congested.
| S-EPMC7668169 | biostudies-literature
Project description:Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes.N/A.Animal sleep research laboratory.Sixty-six C57BL6/J adult mice.Instrumental sleep disruption at a rate of 60/h during 14 days.Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF.Chronic SF increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.
| S-EPMC4355896 | biostudies-other
Project description:Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here, we demonstrated that PR-domain containing protein 13 (Prdm13)+ neurons in the dorsomedial hypothalamus (DMH) are activated during sleep deprivation (SD) in young mice but not in old mice. Chemogenetic inhibition of Prdm13+ neurons in the DMH in young mice promotes increase in sleep attempts during SD, suggesting its involvement in sleep control. Furthermore, DMH-specific Prdm13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during SD. These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep fragmentation and increased sleep attempts during SD, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated increased sleep attempts during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep-wake patterns during aging.
| S-EPMC10105329 | biostudies-literature