Sleep and its oscillatory characteristics in overnight learning - what is the role of plasticity genes BDNF and COMT?

Sleep is crucial for memory function. Sleep not only protects memories from wake-time interference, but it also actively transfers them from temporal storage to more permanent representations in the neocortex. This consolidation process of declarative memories is believed to be facilitated by certain oscillations during non-rapid eye movement (NREM) sleep, that is, sleep spindles, slow oscillations (SO) and sharp-wave ripples. Recent experiments in humans have demonstrated the importance of inter-oscillation synchrony on memory retention. Do all individuals equally share the memory benefits of sleep? Certain gene polymorphisms, such as BDNF Val66Met and COMT Val158Met, have been attributed with implications on synaptic plasticity, neuroanatomy and functional brain activation within memory-related brain networks. Behavioral studies have found relative mnemonic advantages to associate with the alleles that reportedly promote brain plasticity, i.e. ValBDNF and MetCOMT. Moreover, homeostatic sleep drive is moderated by BDNF Val66Met and COMT Val158Met. However, the role of these polymorphisms in memory retention over sleep has been scarcely studied. In this thesis, overnight memory for verbal and visual material was studied. Specific focus was put on how sleep spindles and their phasic synchrony with slow oscillations associate with memory performance. Importantly, it was questioned whether genetic predisposition for neural plasticity (BDNF Val66Met and COMT Val158Met) interacts with overnight memory and the related consolidation mechanisms. The studies in this thesis were conducted either on an adolescent (~17 y) cohort or on a sample consisting of young adults. Sleep was recorded with an ambulatory polysomnography in all studies. It was found that memory outcome – both verbal cued recall and picture recognition – was strongly associated with fast sleep spindles and their accurate coupling with the depolarized ‘upstate’ of SOs. BDNF Val66Met moderated the associations between sleep oscillations and visual recognition memory: memory outcome was robustly predicted by fast sleep spindles and their SO-coupling only in ValBDNF homozygotes but not MetBDNF carriers. In addition, memory performance in the ValBDNF homozygote group was seen more vulnerable to extended wake during the retention period. COMT Val158Met did not moderate the associations between sleep variables and recognition accuracy. In conclusion, the relation between sleep and memory may depend on inheritance. Genetic propensity for synaptic plasticity possibly enhances the effect of events that promote sleep-dependent consolidation. The findings question whether the benefits of sleep on memory are constant and equal across individuals.