by Charité – Universitätsmedizin Berlin

Neurons in the neocortex: Slow-wave sleep strengthens the connections between them, supporting memory formation. Credit: Charité | Sabine Grosser

It has been known for nearly 20 years that slow, synchronous electrical waves in the brain during deep sleep support the formation of memories. Why that is, was previously unknown.

Now, writing in the journal Nature Communications, a team of researchers from Charité—Universitätsmedizin Berlin posits an explanation. According to the study, the slow waves make the neocortex, the location of long-term memory, especially receptive to information. The findings could help to optimize the treatment approaches that are intended to support memory formation from outside.

How do permanent memories form? Experts believe that while we sleep, our brains replay the events of the day, moving information from the location of short-term memory, the hippocampus, to the long-term memory located in the neocortex.

“Slow waves” are especially key to this process: slow, synchronous oscillations of electrical voltage in the cortex that occur during the deep sleep phase. They can be measured using an electroencephalogram (EEG). The waves originate when the electrical voltage in many neurons rises and falls simultaneously 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.”

Ten “feelers” to track deep sleep: This friendly-looking microscope was instrumental in decoding the effects of the slow waves typical of sleep. Equipped with ten glass pipettes that can be controlled precisely down to the nanometer using robot arms, it can stimulate and read the electrical activity of just as many nerve cells in the connected tissue. Credit: Charité | Franz Xaver Mittermaier

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 10 “pipette feelers” at once—an extra large number for this method, which is known as the multipatch technique.

Ten “pipette feelers” in use. Credit: Charité | Yangfan Peng

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.”

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.”

More information: Franz X. Mittermaier et al, Membrane potential states gate synaptic consolidation in human neocortical tissue, Nature Communications (2024). DOI: 10.1038/s41467-024-53901-2

Journal information:Nature Communications

Provided by Charité – Universitätsmedizin Berlin

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