Orexins/hypocretins cause sharp wave- and θ-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling

Selbach, Oliver; Doreulee, Nanuli; Bohla, C; Eriksson, Kent; Sergeeva, Olga A.; Poelchen, Wolfgang; Brown, Ritchie E.; Haas, Helmut L.

doi:10.1016/j.neuroscience.2004.05.012

Cited by 103 publications

(84 citation statements)

References 76 publications

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“…We believe this possibility is unlikely because it has been shown that elevating Hcrt levels by i.v. injection improves learning and memory despite sleep deprivation (34), and application of Hcrt to a hippocampal slice preparation increases long term potentiation (35). Thus, any direct effects of Hcrt on learning would be more likely to augment than to impair it.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic disruption of sleep continuity impairs memory consolidation

Rolls¹,

Colas

Adamantidis³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

126

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Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.nonrapid eye movement sleep | rapid eye movement sleep A lthough much has been learned about how sleep is regulated, there is still no consensus on the function of sleep. One hypothesis is that sleep is needed for memory consolidation (1-5). Testing this hypothesis has been confounded by sleep deprivation methodologies which are drastic manipulations affecting the overall activity of neuronal networks, including cellular energy demand (6, 7), protein synthesis (8), levels of free radicals (9), and specific synaptic changes (10). In many cases sleep deprivation also induces a stress response (11, 12), which itself has been shown to affect memory (4, 13).Some argue that sleep might support memory consolidation by merely providing passive isolation from sensory interruption (14, 15), a claim that cannot be excluded when external sensory stimulation (such as gentle handling or playing a tone) is the method used to disturb sleep. Traditional methods of sleep deprivation disrupt the composition of sleep [percentage of rapid eye movement (REM) and non-REM (NREM) sleep] at the same time as disrupting sleep quality, sleep continuity, and, in most cases, reducing total sleep duration (8,16,17). Thus, it has not been possible to study the role of a specific characteristic of sleep, such as sleep continuity, in memory consolidation.Sleep continuity is affected by different neurological conditions, e.g., sleep apnea, aging, and alcoholism (18,19). The occurrence of memory deficits in many of these conditions raised the question of whether the conti...

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Section: Discussionmentioning

confidence: 99%

Optogenetic disruption of sleep continuity impairs memory consolidation

Rolls¹,

Colas

Adamantidis³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

126

View full text Add to dashboard Cite

show abstract

“…In this context, it is conceivable that substances that play a role in the regulation of sleep and wakefulness could contribute to the changes elicited by SD. Thus, orexin, which promotes arousal (Saper et al, 2005) and modulates hippocampal synaptic plasticity (Selbach et al, 2004), can control rapid NMDAR trafficking via a protein kinase C-dependent mechanism (Borgland et al, 2006). Furthermore, adenosine, which plays an important role in sleep regulation (Obal and Krueger, 2003;Rétey et al, 2005), may modulate glutamatergic receptor function (Sebastiao and Ribeiro, 1996;Dunwiddie and Masino, 2001).…”

Section: Discussionmentioning

confidence: 99%

Insufficient Sleep Reversibly Alters Bidirectional Synaptic Plasticity and NMDA Receptor Function

Kopp¹,

Longordo²,

Nicholson³

et al. 2006

J. Neurosci.

171

145

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Insufficient sleep impairs cognitive functions in humans and animals. However, whether long-term synaptic plasticity, a cellular substrate of learning and memory, is compromised by sleep loss per se remains unclear because of confounding factors related to sleep deprivation (SD) procedures in rodents. Using an ex vivo approach in C57BL/6J mice, we show that sleep loss rapidly and reversibly alters bidirectional synaptic plasticity in the CA1 area of the hippocampus. A brief (ϳ4 h) total SD, respecting the temporal parameters of sleep regulation and maintaining unaltered low corticosterone levels, shifted the modification threshold for long-term depression/long-term potentiation (LTP) along the stimulation frequency axis (1-100 Hz) toward the right. Reducing exposure to sensory stimuli by whisker trimming did not affect the SD-induced changes in synaptic plasticity. Recovery sleep reversed the effects induced by SD. When SD was combined with moderate stress, LTP induction was not only impaired but also occluded. Both electrophysiological analysis and immunoblotting of purified synaptosomes revealed that an alteration in the molecular composition of synaptically activated NMDA receptors toward a greater NR2A/NR2B ratio accompanied the effects of SD. This change was reversed after recovery sleep. By using an unparalleled, particularly mild form of SD, this study describes a novel approach toward dissociating the consequences of insufficient sleep on synaptic plasticity from nonspecific effects accompanying SD in rodents. We establish a framework for cellular models of cognitive impairment related to sleep loss, a major problem in modern society.

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“…Moreover, enhanced cortical EEG delta and theta activity represent the control of neuronal plasticity, and presumably learning and reprocessing of memories [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…Products were separated by thin layer chromatography as described [20]. 32 P-labelled phospholipids were detected by autoradiography.…”

Section: Methodsmentioning

confidence: 99%

Tissue selectivity of insulin detemir action in vivo

et al. 2006

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Aims/hypothesis: Recombinant DNA technology is a useful tool that can be used to create insulin analogues with modified absorption kinetics to improve glycaemic control in patients with type 1 and type 2 diabetes. Among conventional insulin analogues, which are usually created by amino acid exchange, insulin detemir is the first analogue to be acylated with a fatty acid to enable reversible albumin binding. In this study we determined activation of the insulin receptor (IR)-signalling cascade by insulin detemir at the level of IR and IR substrate (Irs) phosphorylation, as well as downstream signalling elements such as phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo. Methods: C57Bl/6 mice were injected i.v. with either insulin detemir or human insulin and Western blot analysis was performed on liver, muscle, hypothalamic and cerebrocortical tissues. Moreover, cerebrocortical activity was detected by EEG in awake mice and cerebral insulin concentrations were measured following human insulin and insulin detemir injection. Results: The time course and extent of IR phosphorylation in peripheral tissues were similar following insulin detemir treatment compared with human insulin, but insulin signalling in hypothalamic and cerebrocortical tissue determined by tyrosine-phosphorylation of the IR and Irs2 proteins occurred faster and was enhanced due to a higher insulin detemir concentration in the brain. Moreover, epidural EEG in mice displayed increased cortical activity using insulin detemir. Conclusions/interpretation: Taken together, these data suggest that insulin detemir has a tissue-selective action, with a relative preference for brain compared with peripheral tissues.

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Orexins/hypocretins cause sharp wave- and θ-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling

Cited by 103 publications

References 76 publications

Optogenetic disruption of sleep continuity impairs memory consolidation

Optogenetic disruption of sleep continuity impairs memory consolidation

Insufficient Sleep Reversibly Alters Bidirectional Synaptic Plasticity and NMDA Receptor Function

Tissue selectivity of insulin detemir action in vivo

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