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

Abstract

BackgroundSleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of NonREM sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. AimsInvestigate the role of metabotropic glutamate receptor 5 (mGluR5) on memory processing during sleep. MethodsIn two placebo-controlled within-subject cross-over 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 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. Results/OutcomesSurprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memoryrelevant 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. Conclusions/InterpretationsOur 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. Declaration of interest/FundingThe authors have nothing to disclose and funders had no influence on the research presented here.