It has been known for almost 20 years that slow, synchronised excitation waves during deep sleep support memory formation. It was previously unknown why this is the case. A research team from Charité – Universitätsmedizin Berlin has now provided an explanation in the journal Nature Communications*. The slow waves make the cerebral cortex, the seat of long-term memory, particularly receptive to information. The findings could contribute to the optimisation of treatment approaches designed to support memory formation from the outside.

Berlin/Germany, December 12th, 2024 How are lasting memories formed? Experts believe that our brain replays the events of the day while we sleep, moving the information from the seat of short-term memory, the hippocampus, to long-term memory in the cerebral cortex. The so-called ‘slow waves’ are particularly important for this memory formation: slow, synchronous waves of excitation in the cerebral cortex that occur in the deep sleep phase and can be measured by electroencephalogram (EEG). They are due to the fact that the electrical voltage of many nerve cells rises and falls simultaneously once per second.

‘We have known for many years that these voltage fluctuations contribute to memory formation,’ explains Prof Jörg Geiger, Director of the Institute of Neurophysiology at Charité and head of the recently published study. ‘This is because artificially reinforcing slow-wave sleep from the outside improves memory performance. Until now, however, we didn’t know what exactly happens in the brain because the flow of information in the human brain is extremely difficult to research.’

Slow waves strengthen synapses

Using particularly rare human brain tissue, he and his team have now succeeded in elucidating the processes that most likely underlie memory formation during deep sleep. According to the findings, the slow waves of excitation influence the strength of the synaptic connections between the nerve cells in the cerebral cortex – and therefore their ability to absorb information.

For the study, the research team examined intact tissue from the cerebral cortex of 45 patients who had undergone neurosurgery to treat epilepsy or a brain tumour at Charité, Bethel Protestant Hospital or the University Medical Centre Hamburg-Eppendorf. The scientists simulated the voltage fluctuations in the tissue that are typical of slow waves during deep sleep and then measured the reaction of the nerve cells. To do this, they used extremely fine glass pipettes, which they attached to individual nerve cells with nanometre precision. In order to listen to the communication of several neurones in the tissue network, they used ten ‘pipette sensors’ simultaneously – a particularly high number for this method, which is known as the multipatch technique.

Perfect timing favours memory formation

The research team discovered that the synaptic connections between the neurons in the cerebral cortex are maximised at a very specific time during the voltage fluctuations. ‘The synapses work most efficiently immediately after the voltage has risen from a low level to a high level,’ explains Franz Xaver Mittermaier, a scientist at Charité’s Institute of Neurophysiology and lead author of the study. ‘Within this short time window, the cerebral cortex is virtually put into a state of heightened readiness. If the brain replays a memory right now, it is transferred particularly effectively into long-term memory. Slow-wave sleep therefore apparently supports memory formation by making the cerebral cortex particularly receptive for many short periods of time.’

It may be possible to use this knowledge to improve memory performance, for example in cases of incipient forgetfulness in old age. Research groups around the world are working on methods to influence the slow waves during sleep using subtle electrical impulses – transcranial electrical stimulation – or acoustic signals. ‘At the moment, however, such stimulation is painstakingly optimised through trial and error,’ says Jörg Geiger. ‘This is where our findings on perfect timing could help. For the first time, they make it possible to specifically develop stimulation methods to support memory.’

*Mittermaier FX et al. Membrane potential states gate synaptic consolidation in human neocortical tissue. Nat Commun 2024 Dec 12. doi: 10.1038/s41467-024-53901-2

Slow excitation waves
Slow waves (also known as ‘slow oscillations’) are slow waves of excitation during deep sleep. The term ‘delta waves’ refers to a specific frequency band in the EEG and thus describes slow excitation waves that can also occur outside of sleep in the context of illnesses. In this respect, it is an umbrella term, but is sometimes used synonymously with ‘slow waves’.

About the study
During surgical treatment of refractory epilepsy or brain tumours, it is often medically necessary to remove small fragments of the cerebral cortex. The tissue can survive in an artificial nutrient solution outside the body for up to two days before it ceases to be active, during which time it can be used for research. The prerequisite for analysing this valuable tissue in the now published study was the explicit consent of the patients, for which the research group would like to express its gratitude. The work was carried out in close collaboration between the basic science and clinical departments of the Charité and the Department of Neurosurgery at the Bethel Protestant Hospital in Bielefeld and the Department of Neurosurgery at the University Medical Centre Hamburg-Eppendorf.

Under the direction of the Institute of Neurophysiology, the following Charité departments were involved: the Department of Neurosurgery, the Department of Neurology with Experimental Neurology, the Institute of Integrative Neuroanatomy, the Neuroscience Research Centre, the NeuroCure Cluster of Excellence, the Department of Paediatric Neurosurgery and the Department of Paediatrics with a focus on neurology.

Translated with DeepL_com


Original publication:

(https://www.nature.com/articles/s41467-024-53901-2)

Further Information:

(https://www.charite.de/service/pressemitteilung/artikel/detail/gedanken_fliessen_in_eine_richtung_statt_in_schleifen/) Charité-Pressemitteilung vom 18.04.2024
(https://neurophysiologie.charite.de/) Institut für Neurophysiologie