Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

Background: Sleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of non-rapid eye movement (NonREM) sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors does not affect sleep-dependent consolidation of declarative memory. Aims: The aim of this study was to investigate the role of metabotropic glutamate receptor 5 (mGluR5) in memory processing during sleep. Methods: In two placebo-controlled within-subject crossover experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II participants learned new word-pairs in the morning after sleep. Results/outcomes: Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memory-relevant EEG oscillations. In NonREM sleep, fenobam suppressed 12–15 Hz spindles but augmented 2–4 Hz delta waves, whereas in rapid eye movement (REM) sleep it suppressed 4–8 Hz theta and 16–22 Hz beta waves. Notably, under fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Conclusions/interpretations: Our findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.

Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

Sleep consolidates declarative memory by the repeated replay of neuronal traces encoded during prior wakefulness. This replay during sleep is linked to the cardinal oscillations of NonREM sleep. Although this replay is ideally suited to support plasticity, there is so far little evidence of classical glutamatergic plasticity playing a role in this process. To the contrary, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. Here, in two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block metabotropic glutamate receptor 5 (mGluR5) during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) during the evening before being administered the treatment and then sleeping for 8 hours – recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep. Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memory-relevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Our findings indicates that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.

0012 REM Sleep in Ostrich Chicks

Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to 5 min) and more REM sleep (24% of the nighttime) than any other avian species. In all mammals studied so far REM sleep predominates at early age suggesting it promotes development of the brain. The aim of this study was to examine REM sleep in ostrich chicks. Methods EEG, electrooculogram and electromyogram of the neck muscles were recorded in 4 chronically implanted 2–3 month old ostrich chicks over 3 nights. The last night was scored in 4-sec epochs for waking, nonREM and REM sleep. Results NonREM sleep and REM sleep in the ostrich chicks occurred when they were sitting or lying with the head held above the ground or rested on the ground. REM sleep was characterized by distinct rapid eye movements, head drops and eye closure. The amplitude of the EEG during episodes of REM sleep ranged between low voltage EEG, as recorded during quiet waking and high voltage slow waves, as recorded during nonREM sleep EEG. The ostrich chicks spent on average 70.7 + 2.2% of the nighttime in nonREM sleep and 12.3 + 3.9% in REM sleep. The episodes of REM sleep lasted on average 9 + 1 sec and ranged between 4 and 36 sec. Conclusion Similar to adult birds, 2–3 mo old ostrich chicks displayed a “mixed” sleep state which has features of both slow wave sleep / nonREM and REM sleep, as we have described in the platypus and echidna. An unexpected result of this study is the total amount and duration of episodes of REM were considerably smaller than has been reported in adult ostriches. More studies need to be done on the developmental and environmental determinants of REM sleep in the ostrich. Support The Russian Foundation for Basic Research (18-04-01252) and HL148574

0445 A Novel Algorithm for the Estimation of Sleep States Based on Breathing and Movement

Introduction We tested the diagnostic accuracy of the novel Nox BodySleep™ algorithm (Nox Medical, Iceland) for the estimation of sleep states from polygraphy (PG) sleep recordings based on features extracted from actigraphy and respiratory inductance plethysmography (RIP) belts. The algorithm automatically classifies epochs into three states, Wake, REM sleep and NonREM sleep. Validation was performed against polysomnography (PSG) in a sleep laboratory collective including patients with sleep disordered breathing (SBAS) and sleep related movements disorders. Methods Patients received PSG according to clinical routine. The recording was evaluated by the novel algorithm and the results were evaluated by descriptive statistics methods (IBM SPSS Statistics 25.0). Results We found a good Spearman correlation (r=0.8) and a bias of 11 minutes for the estimation of Total Sleep Time. Sleep Efficiency was also valued with a good Spearman correlation (r=0.7) and a bias of 1.6%. Wake phases were estimated with a F1 score of 0.64 while REM and Non-REM phases were evaluated with a F1 score of 0.73 and 0.82, respectively. Additionally, an overall accuracy of 0.8 and a Cohens kappa of 0.7 were found. Patients with sleep related movement disorders showed a slighly weaker correlation as patients with SBAS. Conclusion The algorithm shows a good diagnostic accuracy for the estimation of sleep states and significant sleep parameters. After validation on a larger patient collective, it could be used in the ambulatory and telemedical field to allow investigations comparable to the accuracy of a PSG. Support No support.

Fast and slow cortical high frequency oscillations for cortico-cortical and cortico-hippocampal network consolidation during NonREM sleep

Memory reactivation during NonREM-ripples is thought to communicate new information to a systems-wide network. Cortical high frequency events have also been described that co-occur with ripples. Focusing on NonREM sleep after different behaviors, both hippocampal ripples and parietal high frequency oscillations were detected. A bimodal frequency distribution was observed in the parietal high frequency events, faster and slower, with increases in prefrontal directionality measured by Granger causality analysis specifically seen during the fast parietal oscillations. Furthermore, fast events activated prefrontal-parietal cortex whereas slow events activated hippocampal-parietal areas. Finally, there was a learning-induced increase in both number and size of fast high frequency events. These patterns were not seen after novelty exposure or foraging, but occurred after the learning of a new goal location in a maze. Disruption of either sleep or hippocampal ripples impaired long-term memory consistent with these having a role in memory consolidation.