Type 1 diabetes : regenerate our own insulin cells ?

Patrick Collombat, Inserm Research Director and head of the Avenir team at the Institut de Biologie Valrose in Nice, has published new results concerning Type I diabetes. Researchers show that, in mice, the pancreas contains cells capable of being converted into insulin-producing β cells, something that can be done at any age. They also demonstrate that all pancreatic β cells can be regenerated several times and that chemically-induced diabetes in mice can thus be “treated” repeatedly. The challenge for the researchers is now to show that these procedures can be applied to humans.

This work is published online in the Developmental Cell journal dated 27 June 2013.

Type I diabetes, characterised by the selective loss of pancreatic, insulin-producing β cells, is a condition that affects more than 30 million people worldwide. Despite current treatments, type I diabetic patients have a life expectancy that is reduced by five to eight years. It is in this context that the Avenir “Diabetes Genetics” team have been working to develop new approaches designed to regenerate these cells.

In 2009, researchers at the Valrose Biology Institute (Inserm/University Nice Sophia Antipolis) managed to convert glucagon-producing α cells into β cells in young mice. Today, thanks to the use of transgenic mice, they report the mechanisms resulting in this exchange of cell identity. Specifically, they show that pancreatic ductal cells can be continuously mobilised and literally transformed into α and subsequently into β cells, a process that works at any age. Such transformation is obtained through the forced activation of the Pax4 gene in the α cells of the pancreas. The resulting cascade of events causes the generation of brand-new β cells, thanks to the reactivation of development genes. Throughout this process, α cells are regenerated and gradually adopt the profile of β cells. This means that the pancreas has a virtually inexhaustible source of cells capable of replacing the β cells.

β cell regeneration in the pancreas


© Patrick Collombat / Inserm

Left: pancreas of control mice (non-diabetic)
Right: pancreas of transgenic mice demonstrating massive regeneration of insulin-producing β cells (coloured pink) following chemical induction of diabetes.

By artificially inducing type I diabetes in mice, 

“we also show that all the pancreatic β cells can be regenerated at least three times using this mechanism. Diabetes, induced in this way, in the mouse, can be literally “treated” multiple times thanks to the new stock of functional, insulin-producing β cells”

explains Patrick Collombat, Inserm research director and principal author of the study.

These promising results obtained in the mouse suggest that the pancreas contains cells that can regenerate several times those β cells lost in type I diabetics.

“We are currently working on the possibility of inducing such regeneration by using pharmacological molecules. Thanks to this new data, we shall be concentrating in future years on determining whether these processes can also be made to work in humans, a real challenge in offering better treatments for type I diabetic patients”, he concludes.

Stress: it should never be ignored!

Work pressure, tension at home, financial difficulties … the list of causes of stress grows longer every day. There have been several studies in the past showing that stress can have negative effects on health (cardiovascular diseases, diabetes, high blood pressure and more). The Inserm researchers at unit 1018, “The Epidemiology and Public Health Research Centre”, working in collaboration with researchers from England and Finland have demonstrated that it is essential to be vigilant about this and to take it very seriously when people say that they are stressed, particularly if they believe that stress is affecting their health. According to the study performed by these researchers, with 7268 participants, such people have twice as much risk of a heart attack, compared with others.

These results have been published in European Heart Journal.

Today, stress is recognized as one of the main health problems. When people face a situation that is considered stressful, they may experience several physical, emotional and behavioural symptoms (anxiety, difficulty in concentrating, skin problems, migraines, etc.). Previous studies, particularly the recent studies performed within the Whitehall II cohort[1], composed of several thousand British civil servants, have already shown that the physiological changes associated with stress can have an adverse effect on health.

stess au travail

crédit : ©Fotolia

Herman Nabi, Inserm researcher at Unit 1018 “The Epidemiology and Public Health Research Centre”, and his team went further and studied people who declared themselves to be stressed, in order to look more closely at whether there was a link between their feeling and the occurrence of coronary disease some years later.

Using a questionnaire prepared for the Whitehall II cohort, the participants were invited to answer the following question: “to what extent do you consider the stress or pressure that you have experienced in your life has an effect on your health”, the participants had the following answers to choose from: “not at all”, “a little”, “moderately”, “a lot” or “extremely”.

The participants were also asked about their stress level, as well as about other factors that might affect their health, such as smoking, alcohol consumption, diet and levels of physical activity. Arterial pressure, diabetes, body mass index and socio-demographic data such as marital status, age, sex, ethnicity and socio-economic status were also taken into account.

According to the results, the participants who reported, at the start of the study, that their health was “a lot” or “extremely” affected by stress had more than twice the risk (2.12 times higher) of having or dying from a heart attack, compared with those who had not indicated any effect of stress on their health.

From a clinical point of view, these results suggest that the patient’s perception of the impact of stress on their health may be highly accurate, to the extent that it can predict a health event as serious and common as coronary disease.

In addition, this study also shows that this link is not affected by differences between individuals related to biological, behavioural or psychological factors. However, capacities for dealing with stress do differ massively between individuals depending on the resources available to them, such as support from close friends and family.

According to Hermann Nabi, “the main message is that complaints from patients concerning the effect of stress on their health should not be ignored in a clinical environment, because they may indicate an increased risk of developing and dying of coronary disease. Future studies of stress should include perceptions of patients concerning the effect of stress on their health”.

In the future, as Hermann Nabi emphasizes, “tests will be needed to determine whether the risk of disease can be reduced by increasing the clinical attention given to patients who complain of stress having an effect on their health”.


[1] Created in 1985, the Whitehall II cohort, consisting of British civil servants, is making a major contribution to research in social epidemiology and is considered internationally to be one of the main sources of scientific knowledge concerning social determinant factors for health.

Food contaminants worsen metabolic problems in obese mice

Certain food contaminants are suspected of triggering metabolic disorders, or of worsening them, particularly when they accompany a high-fat diet. In order to get a better understanding of these effects, researchers from the Inserm cardiovascular, metabolism, diabetology and nutrition unit (U1060 « Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition » Inserm/Inra/Université Lyon 1) introduced a “cocktail” of contaminants mixed with low doses of dioxin, PCB, bisphenol A and phtalates into the feeding of mice that had already been rendered obese by a high-fat diet. The results show that metabolic changes occur in these mice, but that the effects differ depending on the gender. Females appeared to be more affected. Their obesity-induced glucose intolerance worsened and their estrogen pathway was altered.

These works have been published in the review Faseb Journal.


crédit : ©Fotolia

Obesity is a major public health problem because it is a risk factor in the development of metabolic complications (diabetes, cardiovascular diseases, etc.). It is a multi-factorial disorder. In addition to genetic predispositions and a life style that combines overeating with lack of exercise, there is a great volume of proof to suggest that contaminants, particularly in the food we eat, are responsible for the obesity epidemic and the resulting metabolic changes.

Researchers have put forward the hypothesis that contaminants in food could worsen certain metabolic problems already caused by eating an over-rich or a high-fat diet.

In this study, the researchers fed mice a high-fat diet (already a health risk), to which low doses of contaminants had been added. They were given this diet throughout their lives. Their mother had been nourished with this diet prior to their birth and during the gestation and lactation periods. Therefore, they suffered chronic exposure to this diet.

Two environmentally persistent contaminants[1] (dioxin and PCB) and two non-persistent contaminants[2] (phtalate and bisphenol A) were added to the high-fat (obesogenic) diet of the mice. The doses given were low, normally considered not to have any health impacts.  These products were chosen because they are present in human food and because they are known to trigger endocrine disruption. In parallel, a control group of mice was fed with the same obesogenic diet, but without added contaminants.

The researchers then ran glucose tolerance and insulin sensitivity tests. They measured the livers for lipid accumulation and the expression of certain genes that play key roles in the metabolism of the adult mice.

The results show that the effects are highly dependent on the gender of the animal.

Male and female: different effects

In the females fed with a high-fat diet, the addition of contaminants worsened the glucose intolerance and altered the estrogen pathway. In males, it altered the cholesterol and lipid metabolism. There was no change in weight between the exposed mice and the unexposed mice.

The researchers pursued the hypothesis that there was a connection between the observed glucose intolerance and the alteration in the estrogen signaling in exposed females. It is well known that estrogens protect against metabolic disorders. In other words, these works suggest that in obese females, exposure to food contaminants could lower the protection level that estrogens provide against metabolic disorders.

“With this study, we have succeeded in providing proof-of-concept that low doses of contaminants, even at levels normally considered to be without health impacts in humans, do in fact affect humans when subjected to chronic exposure, and when the contaminants are combined with a high-calorie diet” points out Brigitte Le Magueresse Battistoni.

This study was carried out as part of research programmes supported by the Institut Benjamin Delessert (2010), the ANSES (EST-2010/2/2007) and the EFSD (programme 2011) and by Brigitte Le Magueresse-Battistoni and Danielle Naville, 2 researchers who work for team 1 of the CarMeN Unit run by Hubert Vidal.


[1] These products build up throughout the food chain by means of a process known as bioaccumulation, until they end up on our plates.

[2] These products break down more rapidly that the above, but the intensive production of these products, especially in the plastics industry, means that they are omnipresent in our daily lives.

Pesticides and their effect on health

Since the eighties, epidemiological research has been looking into how pesticides are involved in several pathologies in persons who are exposed to these substances in the course of their work, in particular cancerous pathologies, neurological pathologies and reproductive disorders. These investigations have highlighted the potential effects of even low levels of exposure during the sensitive periods of development (in utero and during childhood).

In this context, the DGS (Direction Générale de la santé – the public health authority) asked Inserm to draw up a list of scientific publications that could be used to corroborate the health risks involved in occupational exposure to pesticides, in particular in agriculture and on the effects of early exposure of the foetus and young children.

In reply to this request, Inserm got together a multidisciplinary group of experts in which epidemiologists specialising in environmental health or occupational health worked alongside biologists specializing in cellular and molecular toxicology.

According to international scientific publications issued over the last 30 years and analysed by these experts, there appears to be a positive link between occupational exposure to pesticides and certain pathologies in adults: Parkinson’s disease, prostate cancer, hematopoietic cancers (non-Hodgkin’s lymphoma, and multiple myeloma).

Furthermore, exposure to pesticides during the prenatal and postnatal periods and in infancy appears to be a particularly risk for the development of the child.

tracteur pesticides


Pesticides: definitions, use and exposure routes

The term ‘pesticide’ comes from the Latin ‘Pestis’ (plague) and Caedere (to kill), and encompasses a large number of widely varying substances that act on living organisms (such as insects, vertebrae, worms, plants, fungi and bacteria) in order to destroy, control or limit them.

There is currently a huge variety of pesticides (around 1000 active substances have already been commercialized, with 309 phytopharmaceutical substances already authorized in France). They vary according to their targets, their modes of action, their chemical class or their persistence in the environment.

– Targets: these include herbicides, fungicides, insecticides, etc.

– There are nearly 100 chemical families of pesticide: organophosphates, organochlorides, carbamates, pyrethrinoids, triazines, etc.

– There are almost 10 000 commercially available formulations of the active substance plus different types of additive (liquid, solid, granules, powders, etc.).

– Pesticides can remain present in the environment from a few hours to several years. They are transformed or degraded into numerous metabolites. Certain of these, such as organochlorides, persist for years in the environment and end up in the food chain.

For the purposes of this study, the term ‘pesticide’ refers to all active substances, independently of regulatory definitions.


Pesticides: what are they used for?

In France, very little quantitative data are available for each type of use. Most of the tonnages (90%) are used for agriculture, but other professional sectors are also concerned: road, garden and park maintenance, the industrial sectors (production, wood treatment), use for human and veterinary health care purposes, vector control (mosquitoes), pest control, etc. We can also add domestic uses to this list (plants, animals, disinfection, gardening, wood).

In France, fungicides represent almost half of the tonnages. 80% of the tonnages of pesticides are used to treat straw cereals, corn, colza and vines. The most commonly sold contain sulphur or glyphosate as the active substance.


Sources of exposure:

Pesticides are present everywhere in the environment. They are present in the air (indoors and outdoors), in water (underground, surface water, coastal waters), in the ground and in foodstuffs (including commercialized bottled water).

In professional environments, the dermal route is the main type of exposure (roughly 80%). Exposure through the respiratory tract occurs in specific application circumstances (during fumigation or when used in closed spaces). Exposure can occur at different times: during handling, preparation, application, cleaning or re-entry (tasks carried out in areas treated with pesticides), but the worst exposure occurs when preparing spray solutions or mixtures or when re-entering already treated areas. For the general population, the oral route is often considered as the main cause of exposure via foodstuffs.


Pesticides and cancers

The group of experts targeted 8 cancer sites: 4 hematopoietic cancers, plus prostate cancer, testicular cancer, brain tumours and melanomas. Most of these sites had been identified in previous meta-analyses as being potentially linked to exposure to pesticides, generally without any distinction having been made between the active substances involved.

  •  Prostate cancer

According to available publications, there is a greater risk to farmers, workers in pesticide manufacturing plants and rural populations (between 12 and 28%, depending on the population). Some active substances have been specifically documented: chlordecone among the general population and carbofuran, coumaphos, fonofos and permethrin among the populations working in associated professions. All these substances are currently prohibited. For certain of them, a higher risk was observed among farmers who had previous family histories of prostate cancer.

  •  Hematopoietic cancers

According to available publications, there is a higher risk of non-Hodgkin’s lymphomas and multiple myelomas for workers exposed to pesticides in the farming and non-farming sectors. Organophosphates and certain organochlorides (lindane, DDT) are thought to be the cause. Although these results are not as convergent, a higher risk of leukaemia cannot be ruled out.

As for the other cancerous sites concerned, it is very difficult to carry out an overall analysis of all the studies. There are several reasons for this: they may occur less frequently (testicular cancer, brain tumours and Hodgkin’s disease), or other factors may lead to confusion (for example, exposure to UVs in the farming population, since UV exposure is a well-known risk factor for melanomas).


Pesticides and neurodegenerative diseases

The group of experts concentrated on 3 neurodegenerative diseases: Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis, and on cognitive disorders, that could be early signs of or be associated with certain neurodegenerative diseases.

  • Parkinson’s disease

An increased risk of developing Parkinson’s disease was observed in persons who were exposed to pesticides in the course of their work. The connection was particularly marked in the case of persons exposed to insecticides and herbicides. Up until now, no connection has been proven with fungicides, however there have been fewer studies on this subject.

The results are more contrasted for the other neurodegenerative diseases. For example, in the case of Alzheimer’s disease, the results from the cohort studies are convergent and reveal that there is a higher risk when the case-control studies are less robust. As for amyotrophic lateral sclerosis, the lack of study data makes it impossible to draw conclusions.

Several reviews and a recent meta-analysis have confirmed the adverse effects of exposure to pesticides in the work place, in particular the effect of organophosphates on cognitive functioning. This effect seemed to be clearer for a person having suffered from previous acute intoxication.


Effects on pregnancy and the development of the child

There now exist numerous epidemiological studies that suggest there is a connection between prenatal exposure to pesticides and the development of the child, both in the medium and long term.

  • Effect of occupational exposure during the prenatal period

Publications suggest that there is a significant increase in the risk of foetal deaths (miscarriages) and an increased risk of congenital malformations when the mother has been exposed in her work place. Other studies suggest adverse effects on fine motor skills, visual acuity, or even short-term memory during the development of the child. Finally, the recent meta-analyses have highlighted a significantly higher risk of leukaemia and brain tumours.

  • Effects of residential exposure during the prenatal period (surrounding environment or domestic uses)

Several case-control and cohort studies show an increased risk of congenital malformations in children born to women living in the vicinity of an agricultural area or involved in the domestic use of pesticides (cardiac malformations, neural tube defects, hypospadias).

Low birth weight, neurodevelopmental disorders and a significant increase in the risk of leukaemia have also been reported.


Pesticides and fertility

The link between certain pesticides (in particular dibromochloropropane) that are no longer used and adverse effects on male fertility has been clearly established, but many uncertainties remain as to pesticides currently in use.

The link between pesticides and female infertility is not well known and needs more in-depth study.


Biological mechanisms

Current publications are insufficient to accurately identify the cellular and molecular mechanisms involved in pathologies that are potentially linked to exposure to certain pesticides. However, certain modes of action of these substances corroborate the epidemiological data. For example, oxidative stress seems to play a major part, in the case of Parkinson’s disease. DNA damage, disturbances in certain signalling pathways (likely to cause a disturbance in cell proliferation or cell death), or alterations to the immune system are all indicative of the effects of pesticides on health.


The problem of pesticide mixtures

Populations are permanently exposed to low doses of pesticides and numerous other substances that contaminate the environment. These mixtures of pesticides and other substances could lead to health risks that are difficult to predict at the current time, and this makes the problem of mixtures and low doses a major issue for research and evaluating dangers.

Experts are pointing out that the fact of being unable to come to a conclusion does not necessarily mean that there is no risk. If certain substances are blamed, it is merely because they have been studied more often than others (in particular, in the United States context); many active substances have not been subjected to epidemiological studies.



The recommendations highlight the need for a better understanding of old and new data concerning populations exposed either directly or indirectly to pesticides in the work place.

The recommendations also draw attention to the critical exposure periods (development periods), both in working environments and in the general population.

Multi- and trans-disciplinary research must be consolidated in order to allow more rapid characterisation of the potential dangers presented by the active substances in pesticides.

Early exposure to bisphenol A might damage the enamel of teeth.

Are teeth the latest victims of bisphenol A? Yes, according to the conclusions of work carried out by the research team led by Ariane Berdal of the Université Paris-Diderot and Sylvie Babajko, Research Director at Inserm Unit 872 “Centre des Cordeliers”. The researchers have shown that the teeth of rats treated with low daily doses of BPA could be damaged by this. Analysis of the damage shows numerous characteristics that are common with a recently identified pathology of tooth enamel that affects roughly 18% of children between the ages of 6 and 8.

These results have been published in the American Journal of Pathology

Bisphenol A (BPA) is a chemical compound used in the composition of plastics and resins. It is used for example to manufacture food containers such as bottles or babies’ bottles. It is also used for the protective films inside drinks cans and food tins, or as developers on sales receipts. Significant amounts of BPA have also been found in human blood, urine, amniotic liquid and placentas. Recent studies have shown that this industrial compound has adverse effects on the reproduction, development and metabolism of laboratory animals. It is strongly suspected of having the same effects on humans.

As a precautionary measure, the manufacture and commercialisation of babies’ bottles containing bisphenol A were prohibited in Europe in January 2011. The prohibition will be extended to all food containers in France as from July 2015.

So this study shows that teeth are the latest in an already long list of victims of BPA.

The Inserm researchers have shown that the incisors of rats treated with low daily doses of BPA (5 microgrammes/kg/day) could be damaged by this.

This effect has also been observed within a development window of no more than 30 days post-birth in rats, thus demonstrating a range of sensitivity to exposure.

Analysis of these teeth showed numerous characteristics that are common with a tooth enamel pathology known as MIH (Molar Incisor Hypomineralisation) that selectively affects first molars and permanent incisors. This enamel pathology is found in roughly 18% of children between the ages of 6 and 8. Children affected by this pathology present with teeth that are hypersensitive to pain and liable to cavities. It is interesting to note that the period during which these teeth are formed (the first years of life) correspond to the period during which humans are most sensitive to bisphenol A.

Amongst the earliest observations made was the appearance of “white marks” on the incisors of rats treated with endocrine disruptors, one of which was bisphenol A (BPA). The researchers decided to define the characteristics of incisors of rats treated with low doses of BPA and to compare these with the characteristics of teeth in humans suffering from MIH

Macroscopic observation of marks on both series of teeth showed similarities, in particular fragile and brittle enamel.

Microscope observation of the enamel showed a significant reduction of the Ca/P and the Ca/C ratios in affected teeth.  This leads to mineral depletion, making the teeth more fragile and more liable to cavities.

Finally, analysis of the proteins present in the tooth matrix of rats showed an increased quantity of enamelin, a key protein for enamel formation, and a buildup of albumin leading to hypomineralisation. Analysis of the expression of key enamel genes highlighted two BPA target genes: enamelin and kallicrein 4.

According to Sylvie Babajko, the latest author of this article, “Insofar as BPA has the same mechanism of action in rats as in men, it could also be a causal agent of MIH. Therefore, teeth could be used as early markers of exposure to endocrine disruptors acting in the same way as BPA and so could help in early detection of serious pathologies that would otherwise have occurred several years later”.

dents enfants


credit : ©Fotolia

(French) : Santé en questions : la drépanocytose, les voies de la guérison

(French) : Cancers du rein, mélanomes de l’œil et mésothéliomes : un gène de prédisposition en commun

Optogenetics is proving to be highly promising in the treatment of obsessive-compulsive disorders

Thanks to work carried out by the Massachusetts Institute of Technology in Boston, Eric Burguière, an Inserm researcher working in the MHI research centre and his co-workers have succeeded in reducing the compulsive behaviour of mice using optogenetics, a technique that combines light stimulation with genetic engineering. By applying light stimulation to highly specific neurons in the brain, the researchers managed to re-establish normal behaviour in mice that had beforehand presented pathological repetitive behaviour similar to that observed in human patients suffering from obsessive-compulsive disorders.

These results are published in the journal Science of June 7th 2013. 

Repetitive behaviour is characterised by a certain number of neuro-psychiatric disorders, in particular obsessive-compulsive disorders, that develop to such an extent that they become a real handicap to daily life (for example, washing hands up to 30 times a day; or checking excessively that a door is locked, etc.). Obsessive-compulsive disorders affect 2 to 3% of the population and in France, it is estimated that over one million persons are affected by this disorder.

The usual treatment for obsessive-compulsive disorders is to use pharmacological treatments (anti-depressants, neuroleptics) and/or behavioural psychotherapy. However, in spite of these therapeutic combinations, severe symptoms persist in around one third of patients. So it is necessary to gain better understanding of the cerebral mechanisms that cause these repetitive behaviour patterns in order to provide better treatment.

Previous neuroimaging studies allowed us to identify dysfunctioning in neuron circuits located between the front of the brain (the orbitofrontal cortex) and more deep-seated cerebral structures (the ganglions at the base on the brain), in certain persons suffering from obsessive-compulsive disorders.

In this new study, Eric Burguière and his co-workers (in the laboratory of Pr. Ann Graybiel in the MIT) concentrated their research on this neuron circuit in order to both examine its function in detail and also to develop an approach to treating obsessive-compulsive disorders in a mutant mouse model.

In these mutant mice, the obsessive behaviour was expressed by repeated grooming all day long, to such an extent that it caused cutaneous lesions.

 From a physiological point of view, these animals are failing to express a protein (caused by the absence of a gene Sapap3) that is normally present in the stratial neuron synapses, a structure that is part of the ganglions at the base of the brain and is involved in functions such as learning sequences, developing habits, or decision-making.

Thanks to these mouse models, initial observations allowed the researchers to show that the emergence of compulsive behaviour in mutant mice was caused by a deficiency in behavioural inhibition. The mice are unable to stop the act of grooming, even when it is no longer necessary. The researchers then used recordings of the neuron activity to show that the dysfunction of communication in the brain between the neocortex and the striatum leads to hyperactivity of stratial neurons in mice.

The use of lighT

In order to check this hypothesis, optogenetics was used. This method consists in modifying the previously identified neurons so as to make them express light-sensitive proteins known as opsins. Since these neuron cells are more sensitive to light, it becomes possible to control their activity by exciting them or inhibiting them using a simple light beam.

When the researchers used light stimulation to excite the neurons in the cortex that send messages to the striatum, the compulsive disorders of the mice were greatly attenuated. On the other hand, when there was no stimulation, the compulsive behaviour recurred.

“Our discoveries show that selective stimulation of the circuit can re-establish normal behaviour in mice that originally presented pathological repetitive behaviour, similar to the type of behaviour observed in certain patients suffering from obsessive-compulsive disorders”, stated Eric Burguière.

This study is promising from a methodological point of view, since it shows that the approach using optogenetics may allow us to identify the role played by neuron circuits in the brain that, if found to be dysfunctional, are liable to cause pathological behaviour.

For researchers, this study has an added interest in the light of its clinical prospects. “I have indeed decided to return to France as part of an Inserm[1] team so that I can run a parallel study on the physiological and behavioural effects of deep cerebral stimulation on patients suffering from obsessive-compulsive disorders, and on mice using the optogenetics technique, in order to get a better understanding of how light stimulation works.”

souris optognétique

©K. Deisseroth, Stanford University

Optogenetics: a recent, highly promising technique

Discovered in the mid 2000’s, optogenetics is a technique that combines both optics and genetic engineering. It consists in genetically modifying certain neuron cells to make them sensitive to light. What is the aim of this? The aim is to remotely activate or inhibit a specific sub-population of neurons using a light beam, and, unlike electrical stimulation, to do it without affecting the surrounding cells. What is the purpose? The purpose is to study the causal relationships between the activity of the targeted brain pathways and the behaviour controlled by these.

[1] BEBG team led by Dr. Luc Mallet at the French Brain and Spinal Institute using funds granted by the FondaMental Foundation.