For nearly two decades, it has been understood that slow, synchronous electrical waves in the brain during deep sleep facilitate memory formation. The precise reasons for this phenomenon had remained elusive until a recent study by researchers from Charité – Universitätsmedizin Berlin, published in Nature Communications, proposed a compelling explanation. They suggest that these slow waves enhance the receptivity of the neocortex—the region responsible for storing long-term memories—making it particularly amenable to retaining information. This insight holds significant potential for refining treatments designed to augment memory formation externally.
Memory consolidation is believed to occur during sleep through replaying daily events. This process transfers information from short-term storage in the hippocampus to long-term storage in the neocortex. Central to this process is the “slow waves,” or slow, synchronous oscillations of electrical voltage in the cortex, evident during the deep sleep phase. These can be detected through electroencephalogram (EEG) testing, where the electrical voltage across numerous neurons rises and falls in unison about once per second.
Prof. Jörg Geiger, director of the Institute of Neurophysiology at Charité and study leader, notes that these voltage fluctuations have long been recognized as instrumental in memory development. Enhancing slow-wave sleep externally has been shown to improve memory. Still, the internal mechanics—how the brain’s information flows during this phase—have been challenging to pinpoint due to the complexities of studying human brain activity directly.
The recent breakthroughs in this area have come from the analysis of intact human brain tissue, a rarity in neurological research. The study team examined neocortical tissue samples from 45 patients who underwent neurosurgery for epilepsy or brain tumours at various medical centres. By simulating the typical voltage fluctuations of slow brain waves during deep sleep on these tissues and measuring neuronal responses with precision, using glass micropipettes and the multipatch technique—a method involving multiple “pipette feelers” to monitor inter-neuronal communication—they were able to observe how slow waves affect synaptic strength and neuron receptivity in the neocortex.
The researchers discovered that synaptic connections between neurons in the neocortex are maximally strengthened at a precise moment during voltage fluctuations. Franz Xaver Mittermaier, a researcher at the Institute of Neurophysiology at Charité and the study’s primary author, explained that synapses are most efficient immediately after the voltage spikes from low to high. This brief period is when the cortex appears to be in an enhanced state of readiness. If the brain replays a memory at this exact moment, it is particularly effectively transferred to long-term memory. Thus, slow-wave sleep not only facilitates memory formation but does so by making the neocortex uniquely receptive during these fleeting intervals.
This newfound understanding has profound implications for improving memory, particularly in conditions like mild cognitive impairment among older adults. Researchers globally are exploring how to employ transcranial electrostimulation or acoustic signals to modulate slow waves during sleep. Although these stimulation techniques have traditionally been developed through trial and error, insights from this study about optimal timing could revolutionize these approaches, enabling the targeted development of memory enhancement methods. Prof. Geiger highlighted that these findings pave the way for more efficient, evidence-based strategies in memory treatment, potentially transforming therapeutic practices and improving cognitive health outcomes.
More information: Franz X. Mittermaier et al, Membrane potential states gate synaptic consolidation in human neocortical tissue, Nature Communications. DOI: 10.1038/s41467-024-53901-2
Journal information: Nature Communications Provided by Charité – Universitätsmedizin Berlin
