Genetic Evidence for a Role of CREB in Sustained Cortical Arousal

2003 ◽  
Vol 90 (2) ◽  
pp. 1152-1159 ◽  
Author(s):  
Laurel A. Graves ◽  
Kevin Hellman ◽  
Sigrid Veasey ◽  
Julie A. Blendy ◽  
Allan I. Pack ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Genetic Alterations ◽  
Memory Storage ◽  
Cortical Arousal ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Phosphorylated Creb ◽  
Activity Dependent

The cyclic AMP-response element binding protein (CREB) is an activity-dependent transcription factor important for synaptic plasticity and memory storage. Levels of phosphorylated CREB within the cortex are higher in waking than in sleep, suggesting that CREB plays a role in sleep/wake regulation in mammals. We tested the hypothesis that CREB is critical for sleep/wake regulation by examining behavioral state parameters in mice lacking the α and Δ isoforms of CREB. Over 24 h, time spent awake was significantly decreased in CREB αΔ mutant mice by approximately 100 min, and time spent in nonrapid eye movement sleep (NREM) sleep was increased correspondingly. Wake and REM sleep periods were shorter in CREB αΔ mice, and CREB αΔ mice had decreased levels of θ-activity during wake and REM sleep, consistent with an impairment in the ability to maintain an activated electroencephalogram. These results suggest that the CREB protein contributes to the mechanisms by which wakefulness is maintained and demonstrate that specific genetic alterations in species as diverse as Drosophila and mice produce similar phenotypes in arousal and wakefulness.

scholarly journals CREB is Required in Excitatory Neurons in the Forebrain to Sustain Wakefulness

2020 ◽  
Author(s):  
Mathieu E. Wimmer ◽  
Cui Rosa ◽  
Jennifer M. Blackwell ◽  
Ted Abel
Keyword(s):  
Cyclic Amp ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Nrem Sleep ◽  
Creb Phosphorylation ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Phosphorylated Creb ◽  
And Control ◽  
Activity Dependent

AbstractThe molecular and intracellular signaling processes that control sleep and wake states remain largely unknown. A consistent observation is that the cyclic-AMP response element binding protein (CREB), an activity-dependent transcription factor, is differentially activated during sleep and wakefulness. CREB is phosphorylated by the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway as well as other kinases, and phosphorylated CREB (pCREB) promotes transcription of target genes. Genetic studies in flies and mice suggest that CREB signaling influences sleep/wake states by promoting and stabilizing wakefulness. However, it remains unclear where in the brain CREB is required to drive wakefulness. In rats, CREB phosphorylation increases in the cerebral cortex during wakefulness and decreases during sleep, but it is not known if this change is functionally relevant to the maintenance of wakefulness. Here, we used the cre/lox system to conditionally delete CREB in the forebrain and in the locus coereleus (LC), two regions known to be important for the production of arousal and wakefulness. We used polysomnography to measure sleep/wake levels and sleep architecture in conditional CREB mutant mice and control littermates. We found that forebrain-specific deletion of CREB decreased wakefulness and increased non-rapid eye movement (NREM) sleep. Mice lacking CREB in the forebrain were unable sustain normal periods of wakefulness. On the other hand, deletion of CREB from LC neurons did not change sleep/wake levels or sleep/wake architecture. Taken together, these results suggest that CREB is required in neurons within the forebrain but not in the LC to promote and stabilize wakefulness.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

scholarly journals Dream Recall upon Awakening from Non-Rapid Eye Movement Sleep in Older Adults: Electrophysiological Pattern and Qualitative Features

2020 ◽  
Vol 10 (6) ◽  
pp. 343 ◽  
Author(s):  
Serena Scarpelli ◽  
Aurora D’Atri ◽  
Chiara Bartolacci ◽  
Maurizio Gorgoni ◽  
Anastasia Mangiaruga ◽  
...  
Keyword(s):  
Eye Movement ◽  
Sleep Stage ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Dream Recall ◽  
Cortical Arousal ◽  
Beta Power ◽  
Dream Report

Several findings support the activation hypothesis, positing that cortical arousal promotes dream recall (DR). However, most studies have been carried out on young participants, while the electrophysiological (EEG) correlates of DR in older people are still mostly unknown. We aimed to test the activation hypothesis on 20 elders, focusing on the Non-Rapid Eye Movement (NREM) sleep stage. All the subjects underwent polysomnography, and a dream report was collected upon their awakening from NREM sleep. Nine subjects were recallers (RECs) and 11 were non-RECs (NRECs). The delta and beta EEG activity of the last 5 min and the total NREM sleep was calculated by Fast Fourier Transform. Statistical comparisons (RECs vs. NRECs) revealed no differences in the last 5 min of sleep. Significant differences were found in the total NREM sleep: the RECs showed lower delta power over the parietal areas than the NRECs. Consistently, statistical comparisons on the activation index (delta/beta power) revealed that RECs showed a higher level of arousal in the fronto-temporal and parieto-occipital regions than NRECs. Both visual vividness and dream length are positively related to the level of activation. Overall, our results are consistent with the view that dreaming and the storage of oneiric contents depend on the level of arousal during sleep, highlighting a crucial role of the temporo-parietal-occipital zone.

scholarly journals Role of Cyclic AMP Response Element–Binding Protein in Insulin-like Growth Factor-I Receptor Up-regulation by Sex Steroids in Prostate Cancer Cells

2009 ◽  
Vol 69 (18) ◽  
pp. 7270-7277 ◽  
Author(s):  
Marco Genua ◽  
Giuseppe Pandini ◽  
Diego Sisci ◽  
Gabriella Castoria ◽  
Marcello Maggiolini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cyclic Amp ◽  
Cancer Cells ◽  
Sex Steroids ◽  
Prostate Cancer Cells ◽  
Factor I ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element

scholarly journals Role of hippocampal NF-κB and GluN2B in the memory acquisition impairment of experiences gathered prior to cocaine administration in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosa López-Pedrajas ◽  
Inmaculada Almansa ◽  
María V. Sánchez-Villarejo ◽  
Borja Muriach ◽  
Jorge M. Barcia ◽  
...  
Keyword(s):  
Drug Administration ◽  
Memory Impairment ◽  
Present Report ◽  
Active Form ◽  
Cocaine Administration ◽  
Chronic Cocaine ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Memory Acquisition

AbstractCocaine can induce severe neurobehavioral changes, among others, the ones involved in learning and memory processes. It is known that during drug consumption, cocaine-associated memory and learning processes take place. However, much less is known about the effects of this drug upon the mechanisms involved in forgetting.The present report focuses on the mechanisms by which cocaine affects memory consolidation of experiences acquired prior to drug administration. We also study the involvement of hippocampus in these processes, with special interest on the role of Nuclear factor kappa B (NF-κB), N-methyl-D-aspartate glutamate receptor 2B (GluN2B), and their relationship with other proteins, such as cyclic AMP response element binding protein (CREB). For this purpose, we developed a rat experimental model of chronic cocaine administration in which spatial memory and the expression or activity of several proteins in the hippocampus were assessed after 36 days of drug administration. We report an impairment in memory acquisition of experiences gathered prior to cocaine administration, associated to an increase in GluN2B expression in the hippocampus. We also demonstrate a decrease in NF-κB activity, as well as in the expression of the active form of CREB, confirming the role of these transcription factors in the cocaine-induced memory impairment.

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