The Circadian Clock Gene Csnk1e Regulates Rapid Eye Movement Sleep Amount, and Nonrapid Eye Movement Sleep Architecture in Mice

Zhou, Lili; Bryant, Camron D.; Loudon, A. S. I.; Palmer, Abraham A.; Vitaterna, Martha Hotz; Turek, Fred W.

doi:10.5665/sleep.3590

Cited by 21 publications

(14 citation statements)

References 43 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study shows the ability of gabapentin to increase baseline von Frey thresholds in naïve mice from the two progenitor strains, indicating that Cacna2d1 is a reasonable candidate gene for basal mechanosensation, and that the effect is genotype-dependent as expected from previous studies (Chesler et al 2003a; Rode et al 2007; Zhou et al 2014). Prior studies have shown that Cacna2d1 expression is increased in the DRG and dorsal horn of the spinal cord after nerve injury (Costigan et al 2002; Field et al 2000, 2006; Luo et al 2002; Matsumoto et al 2006) and this increase has been shown to be essential to the development of mechanical, but not thermal, hypersensitivity after nerve injury (Patel et al 2013).…”

Section: Discussionsupporting

confidence: 82%

“…The neuropathic pain medications gabapentin and pregabalin reduce neuronal excitability and neurotransmission of affected neurons by acting at the VGCC 2 / 1 subunit encoded by Cacna2d1, and thereby, counter mechanical allodynia in neuropathic pain patients and animal models of neuropathic pain (Bian et al 2006;Field et al 2000Field et al , 2006Joshi & Taylor 2006). This study shows the ability of gabapentin to increase baseline von Frey thresholds in naïve mice from the two progenitor strains, indicating that Cacna2d1 is a reasonable candidate gene for basal mechanosensation, and that the effect is genotype-dependent as expected from previous studies (Chesler et al 2003a;Rode et al 2007;Zhou et al 2014). Prior studies have shown that Cacna2d1 expression is increased in the DRG and dorsal horn of the spinal cord after nerve injury (Costigan et al 2002;Field et al 2000Field et al , 2006Luo et al 2002;Matsumoto et al 2006) and this increase has been shown to be essential to the development of mechanical, but not thermal, hypersensitivity after nerve injury (Patel et al 2013).…”

Section: Discussionsupporting

confidence: 64%

See 1 more Smart Citation

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test

Young

Bryant

Lee

et al. 2016

Genes Brain and Behavior

View full text Add to dashboard Cite

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 64%

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test

Young

Bryant

Lee

et al. 2016

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…The hourly mean number of bouts is not shown but can be inferred from the other metrics. In general, the profiles are very similar to those seen in the literature (Brankačk et al 2010, Martire et al 2012, Zhou et al 2014). …”

Section: Resultssupporting

confidence: 85%

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor

Yaghouby

Donohue

O’Hara

et al. 2016

Journal of Neuroscience Methods

View full text Add to dashboard Cite

Background Changes in autonomic control cause regular breathing during NREM sleep to fluctuate during REM. Piezoelectric cage-floor sensors have been used to successfully discriminate sleep and wake states in mice based on signal features related to respiration and other movements. This study presents a classifier for noninvasively classifying REM and NREM using a piezoelectric sensor. New Method Vigilance state was scored manually in 4-second epochs for 24-hour EEG/EMG recordings in twenty mice. An unsupervised classifier clustered piezoelectric signal features quantifying movement and respiration into three states: one active; and two inactive with regular and irregular breathing respectively. These states were hypothesized to correspond to Wake, NREM, and REM respectively. States predicted by the classifier were compared against manual EEG/EMG scores to test this hypothesis. Results Using only piezoelectric signal features, an unsupervised classifier distinguished Wake with high (89% sensitivity, 96% specificity) and REM with moderate (73% sensitivity, 75% specificity) accuracy, but NREM with poor sensitivity (51%) and high specificity (96%). The classifier sometimes confused light NREM sleep—characterized by irregular breathing and moderate delta EEG power—with REM. A supervised classifier improved sensitivities to 90, 81, and 67% and all specificities to over 90% for Wake, NREM, and REM respectively. Comparison with Existing Methods Unlike most actigraphic techniques, which only differentiate sleep from wake, the proposed piezoelectric method further dissects sleep based on breathing regularity into states strongly correlated with REM and NREM. Conclusions This approach could facilitate large-sample screening for genes influencing different sleep traits, besides drug studies or other manipulations.

show abstract

“…While evidence suggests that some of these genes, such as Sik3, have nonoverlapping effects on sleep or circadian systems, there are also variants of genes that not only regulate circadian rhythms (e.g., PER3) but also can modulate sleep (Viola et al 2007). Hinting at how this may disclose neural circuitry that converges between sleep and timing systems, ablation of clock genes (e.g., in CLOCK mutant mice) (Naylor et al 2000) or circadian-associated genes such as Vip also alters sleep duration or structure (Naylor et al 2000;Wisor et al 2002;Laposky et al 2005;Hu et al 2011;Zhou et al 2014). However, in many such studies conducted to date, the genetic targeting has been unspecific with regard to the involved cell types and timing of the deletion (to exclude developmental effects).…”

Section: Overlapping Genetics Of Sleep and Circadian Rhythms?mentioning

confidence: 99%

Neurogenetic basis for circadian regulation of metabolism by the hypothalamus

2019

View full text Add to dashboard Cite

Circadian rhythms are driven by a transcription-translation feedback loop that separates anabolic and catabolic processes across the Earth's 24-h light-dark cycle. Central pacemaker neurons that perceive light entrain a distributed clock network and are closely juxtaposed with hypothalamic neurons involved in regulation of sleep/wake and fast/feeding states. Gaps remain in identifying how pacemaker and extrapacemaker neurons communicate with energy-sensing neurons and the distinct role of circuit interactions versus transcriptionally driven cellautonomous clocks in the timing of organismal bioenergetics. In this review, we discuss the reciprocal relationship through which the central clock drives appetitive behavior and metabolic homeostasis and the pathways through which nutrient state and sleep/wake behavior affect central clock function. Molecular dynamics of the circadian clock[

show abstract

The Circadian Clock Gene Csnk1e Regulates Rapid Eye Movement Sleep Amount, and Nonrapid Eye Movement Sleep Architecture in Mice

Abstract: These results demonstrate a role for Csnk1e in regulating not only the timing of sleep, but also the REM sleep amount and NREM sleep architecture, and support Csnk1e as a causal gene in the sleep QTL on chromosome 15.

Cited by 21 publications

References 43 publications

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor

Neurogenetic basis for circadian regulation of metabolism by the hypothalamus

Contact Info

Product

Resources

About