Inserm Newsroom - Press room of the French national institute of health and medical research

“Nested sequences”: an indispensable mechanism for forming memories

A research team from CNRS, Université PSL, the Collège de France and Inserm has just lifted part of the veil surrounding brain activity during sleep. Though we know that some neurons are reactivated then to consolidate our memories, we did not know how these cells could “remember” which order to turn on in. The researchers have discovered that reactivating neurons during sleep relies on activation that occurs during the day: “nested” theta sequences. These results were published on November 9, 2018 in Science.
Repetition is the best method for memorization, for neurons themselves. This is the principle behind what neurobiologists call sequence reactivations: during sleep, neurons in the hippocampus related to a task activate very quickly in turn in a precise order, which consolidates the memory of this task. Sequence reactivations are fundamental for long-term memorization and for exchanges between the hippocampus and the rest of the brain. These are only present at rest so they appear after initial neuron activity, which implies that they “memorize” the order they should turn on in. But by which mechanism?
A team of researchers from the Centre interdisciplinaire de recherche en biologie (CNRS/Inserm/Collège de France)1 has answered this question by studying activity sequences in rats’ place cells. These are hippocampal neurons that turn on by following the animal’s position in the environment when it moves. First slowly, while it moves, then very quickly during reactivations of sequences during sleep. But neurobiologists know another type of sequence, called theta sequences, which quickly repeat the activation of the same place cells when the animal moves, in parallel with slow sequences. These theta sequences are therefore called “nested”.
Which of these sequences, slow or nested, is necessary for the appearance of sequence reactivations, and therefore causes the consolidation of memories during sleep? Using an ingenious system, the researchers discovered what deactivates nested sequences, without affecting slow sequences: the animals are transported on an electric train, in a car with a treadmill (see image). When the treadmill is stopped, the nested sequences disappear; they return when the treadmill starts again.
The researchers then observed that after several circuits in the train with the treadmill stopped, place cells in the rats’ hippocampi did not reactivate during sleep in the same order as when awake. On the contrary, after one train circuit with the treadmill on, the sequence reactivations are indeed present. So it is these nested theta sequences during movement that are indispensable for the consolidation of memory during sleep.
The researchers are continuing their work, looking now at the integration of non-spatial information such as objects or textures in nested sequences, and their reactivation during sleep.

1. Associated member of the Université PSL, since 2009 the Collège de France has been conducting a voluntaristic policy for welcoming independent teams that benefit from pooled technical or scientific services and an exceptional multidisciplinary environment. Twenty-two teams are currently housed in the Centre interdisciplinaire de recherche en biologie and in the Instituts de chimie et de physique du Collège de France. Supported by the CNRS in particular, this is available to both French and foreign researchers. It contributes to making Paris a major player as an attractive place for research.

Bile acid receptor controls hepatitis B virus replication

Researchers from CIRI – International Center for Research in Infectious Diseases in Lyon (Inserm, CNRS, ENS Lyon and Claude Bernard Lyon 1 University), supported by the ANRS, are demonstrating the link between activation of a bile acid receptor found in liver cells and the reduction in hepatitis B virus replication in mice infected with the virus.

Large Numbers of Older Adults Are Thought to Wear Unsuitable Glasses

Researchers from Inserm, Université de Bordeaux and Sorbonne Université have published a study showing that, out of a population of older adults, nearly 40 % have a poorly-corrected vision problem (such as nearsightedness, farsightedness and astigmatism) which could be improved by wearing more suitable glasses. These findings have been published in JAMA Ophthalmology.

Expédition 5300: a scientific expedition to the world’s highest settlement

A group of over fifteen scientists, led by Samuel Vergès, an Inserm researcher from the “Hypoxia and Cardiovascular and Respiratory Physiopathologies” group (Inserm/Université Grenoble Alpes), is taking part in a scientific expedition to investigate the effect of low oxygen levels on health. In early 2019 they will spend 6 weeks in the world’s highest settlement, situated in Peru at an altitude of 5,300 m, studying how its inhabitants have adapted physiologically to extreme living conditions and analyzing the specific altitude-related health problems they face. Eventually, the researchers hope to use the data in order to improve the understanding and treatment of diseases related to low oxygen levels.

Development of an alternative to bone grafting for edentate patients

Decreased jaw bone volume in edentate patients is the main difficulty which arises when fitting dental implants. Bone grafting is currently the most frequent solution for this problem. However, this method has several disadvantages, such as deterioration of the bone graft over time. Between 2010 and 2015, Pierre Layrolle, Inserm researcher, working with Norwegian and German teams as part of the REBORNE European project, tested an innovative technique for bone augmentation in 11 edentate patients, by combining a biomaterial with stem cells. The results, published in the journal Stem Cell Research & Therapy, demonstrate sufficient growth of viable bone in the treated area to allow implants to be fitted, together with the durable preservation of this bone after fitting dental prostheses.

An Unbalanced Maternal Diet Affects the Digestive System of Offspring

Inadequate protein intake in a gestating female is linked to lasting digestive abnormalities in her offspring. When studying the link between perinatal malnutrition and digestive system in rats, a team of researchers from Inserm in conjunction with Inra, Université de Nantes and University Hospital Nantes discovered functional digestive abnormalities in young rats and an inappropriate response to stress. Although conducted in animals, this research once again demonstrates the incidence of perinatal stress on health in adulthood and draws our attention to the impacts of restrictive diet-related or involuntary deficiencies during pregnancy. This research has been published in The FASEB Journal.

Fewer cases of cancer in organic food consumers?

A 25% reduction in cancer risk has been observed among “regular” organic food consumers, compared to consumers who eat organic less often. These were the findings of an epidemiological study conducted by a team from Inra, Inserm, University of Paris 13, CNAM, following analysis of a sample of 68,946 participants in the NutriNet‐Santé cohort.

Identifying a genetic factor causing lung fibrosis complicating rheumatoid arthritis

Teams of rheumatology, respiratory medicine, genetics and the university hospital department FIRE Hospital Bichat Claude Bernard AP-HP, in collaboration with INSERM, Université Paris Diderot, the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, have discovered that a rare allele of rs35705950 variant gene MUC5B multiply by six the risk of occurrence of pulmonary fibrosis in patients with rheumatoid arthritis (RA). This broad study of genetic association demonstrates the existence of a common genetic basis between pulmonary fibrosis associated with rheumatoid arthritis and idiopathic pulmonary fibrosis (IPF).

These results, obtained with the participation of national and international network of pulmonologists and rheumatologists, are published in the journal The New England Journal of Medicine October 20, 2018.

They are a first step in understanding the diffuse interstitial lung disease (PID) of rheumatoid arthritis, a serious complication whose therapeutic management is not currently codified.

Outbreak of multidrug-resistant tuberculosis undetected by standard tests

Amid a plan announced by the United Nations to eradicate tuberculosis by 2030, a new study has revealed the emergence of multidrug-resistant strains of the disease which go undetected by WHO-endorsed tests. These findings, from an international research team co-directed by CNRS researcher Philip Supply at the Center of Infection and Immunity of Lille (CNRS/INSERM/Institut Pasteur de Lille/Université de Lille), are published in the 17 October 2018 edition of The Lancet Infectious Diseases. This follows another article, published in the 26 September edition of The New England Journal of Medicine, proposing a new algorithm to detect resistant strains of tuberculosis.

Tools: Sensory Organs in Their Own Right ?

What if by holding a tool we could perceive our environment through touch – using the whole tool, and not just the tip? A study by Inserm researchers at the Lyon Neuroscience Research Center (Inserm/Université Jean Monnet Saint-Etienne/Université Claude Bernard Lyon 1/CNRS) has shown just that – the capacity of the human brain to incorporate a tool as an actual sensory organ. This research, published in Nature, raises the question of a new paradigm concerning the sense of touch, its interpretation when developing our use of tools, and in its medical applications – particularly prosthetics.