Slow-wave sleep plays a crucial role in strengthening memory by enhancing synaptic connections in the brain, with new findings suggesting potential methods for boosting memory through targeted stimulation.
For nearly two decades, scientists have known that slow, synchronized electrical waves in the brain during deep sleep play a key role in forming memories. However, the underlying reason remained unclear — until now. In a new study published in Nature Communications, researchers from Charité – Universitätsmedizin Berlin propose an explanation. They found that these slow waves make the neocortex, the brain’s long-term memory center, especially receptive to new information. This discovery could pave the way for more effective memory-enhancing treatments in the future.
How Memories Form During Sleep
How do lasting memories form? Scientists believe that while we sleep, the brain replays events from the day, transferring information from the hippocampus, where short-term memories are stored, to the neocortex, where long-term memories reside. A key player in this process is “slow waves” — synchronized electrical oscillations in the cortex that occur during deep sleep. These waves, which can be measured with an electroencephalogram (EEG), happen when the electrical activity in large groups of neurons rises and falls together about once per second.
“We’ve known for many years that these voltage fluctuations contribute to the formation of memory,” explains Prof. Jörg Geiger, director of the Institute of Neurophysiology at Charité and the head of the newly published study. “When slow-wave sleep is artificially augmented from outside, memory improves. But what we didn’t know until now was what exactly is happening inside the brain when this occurs, because it is extremely difficult to study the flows of information inside the human brain.”
Slow waves, or slow oscillations, are a type of electrical wave arising in the brain during deep sleep. “Delta” waves comprise a certain frequency range that shows up in an EEG. These are slow brain waves that can arise outside sleep as well, as part of a disease or disorder. This broader term is sometimes used synonymously with the term “slow waves.”
Slow Waves Strengthen Synapses
He and his team have now used intact human brain tissue, which is extremely rare, to clarify the processes that are very likely to underlie the formation of memory during deep sleep. According to their findings, the slow electrical waves influence the strength of synaptic connections between the neurons in the neocortex – and thus their receptivity.
For their study, the team of researchers studied intact neocortical tissue samples taken from 45 patients who had undergone neurosurgery to treat epilepsy or a brain tumor at Charité, the Evangelisches Klinikum Bethel (EvKB) hospital, or the University Medical Center Hamburg-Eppendorf (UKE). The researchers simulated the voltage fluctuations typical of slow brain waves during deep sleep in the tissue and then measured the nerve cells’ response. To achieve this, they used glass micropipettes positioned precisely down to the nanometer. To “listen in” on the communications among multiple nerve cells connected through the tissue, they used up to ten “pipette feelers” at once – an extra large number for this method, which is known as the multipatch technique.
Perfect Timing Contributes to Memory Formation
The team of researchers discovered that the synaptic connections between neurons in the neocortex are maximally enhanced at a very specific point in time during the voltage fluctuations.
“The synapses work most efficiently immediately after the voltage rises from low to high,” explains Franz Xaver Mittermaier, a researcher at the Institute of Neurophysiology at Charité and the first author of the study. “During that brief time window, the cortex can be thought of as having been placed in a state of elevated readiness. If the brain plays back a memory at exactly this time, it is transferred to long-term memory especially effectively. So, slow-wave sleep evidently supports memory formation by making the neocortex particularly receptive for many short periods of time.”
Potential for Memory Improvement
This knowledge could be used to improve memory, for example in mild cognitive impairment in the elderly. Research groups around the world are working on methods of using subtle electrical impulses – transcranial electrostimulation – or acoustic signals to influence slow waves during sleep.
“Right now, though, these stimulation approaches are being optimized through trial and error, which is a laborious and time-consuming process,” Geiger says. “Our findings about the perfect timing could help with this. Now, for the first time, they allow for targeted development of methods of stimulation to boost memory formation.”
Reference: “Membrane potential states gate synaptic consolidation in human neocortical tissue” by Franz X. Mittermaier, Thilo Kalbhenn, Ran Xu, Julia Onken, Katharina Faust, Thomas Sauvigny, Ulrich W. Thomale, Angela M. Kaindl, Martin Holtkamp, Sabine Grosser, Pawel Fidzinski, Matthias Simon, Henrik Alle and Jörg R. P. Geiger, 12 December 2024, Nature Communications.
DOI: 10.1038/s41467-024-53901-2
*Mittermaier F. X. et al. Membrane potential states gate synaptic consolidation in human neocortical tissue. Nat Commun 2024 Dec 12. doi: 10.1038/s41467-024-53901-2
About the Study
During surgeries for drug-resistant epilepsy or brain tumors, small fragments of the neocortex sometimes need to be removed for medical reasons. These resected tissue samples can remain viable for up to two days outside the body when preserved in an artificial nutrient solution. For this study, explicit patient consent was required to examine these valuable samples, and the research team expressed profound gratitude to the patients who participated.
The study was a collaborative effort, uniting basic research and clinical expertise. It involved Charité – Universitätsmedizin Berlin, the University Clinic for Neurosurgery at Evangelisches Klinikum Bethel (EvKB) in Bielefeld, and the Department of Neurosurgery at the University Medical Center Hamburg-Eppendorf (UKE). Led by the Institute of Neurophysiology, Charité’s contributions included the Department of Neurosurgery, the Department of Neurology with Experimental Neurology, the Institute of Integrative Neuroanatomy, the Neuroscience Research Center, the NeuroCure Cluster of Excellence, the Division of Pediatric Neurosurgery, and the Department of Pediatric Neurology.
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