Institut du Cerveau https://institutducerveau-icm.org Mon, 21 Sep 2020 15:19:22 +0000 https://wordpress.org/?v=4.9.13 hourly 1 https://wordpress.org/?v=4.9.13 RICHARD MILLE STRENGTHENS HIS COMMITMENT TO THE PARIS BRAIN INSTITUTE https://institutducerveau-icm.org/en/actualite/richard-mille-strengthens-his-commitment-to-the-paris-brain-institute/ https://institutducerveau-icm.org/en/actualite/richard-mille-strengthens-his-commitment-to-the-paris-brain-institute/#respond Thu, 17 Sep 2020 13:58:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19919 Richard Mille, new member of the Paris Brain Institute's Campaign Committee, mobilizes his company and supports actions to finance research programs and increase the For more information ]]> Richard Mille, new member of the Paris Brain Institute’s Campaign Committee, mobilizes his company and supports actions to finance research programs and increase the Institute’s visibility.

The first event that symbolizes this mobilization is the 24 Hours of Le Mans.

 

  •  1st 24 Hours of Le Mans for the Richard Mille Racing Team 
  • 100% Female crew composed of Tatiana Calderón, Sophia Floersch and Beitske Visser 
  • The race is dedicated to the Paris Brain Institute

Speed records may or may not be broken next weekend at Le Mans. Stereotypes, on the other hand, definitely will! The Richard Mille Racing Team, an all-female driver line-up is revving up this, the 88th edition of the world’s most famous motor race. 

[…]

‘Since the creation of this institute in Paris some 10 years ago it has grown to become one of the leading research centres for brain and spinal illnesses that can touch each and every one of us by the sheer magnitude of all those affected. This institute is the 2nd largest in the world dedicated to this cause and gathers very experienced researchers from all corners of the globe. My friendship towards Professor Gérard Saillant and Jean Todt only strengthens my commitment to this cause and to bring it to the attention of all those close to the brand so that as many people as possible are aware of this institute and its quest to cure the multiple diseases linked to the brain,’ explains Richard Mille.

 

 ‘I would like to warmly thank Richard Mille for his renewed support to the Paris Brain Institute through his first participation in the 24 Heures du Mans with an all-female team. This unique sporting competition embodies values of combativeness, perseverance and excellence that the Paris Brain Institute fully shares. Richard Mille’s commitment at our side represents a great strength for us, as it allows us to further develop the means of our ambitions, to increase the visibility of our commitment to an essential public health cause and gives our researchers the opportunity to go even further in their research work at the service of patients’. – Professor Gérard Saillant, President of the Paris Brain Institute.

Read Richard Mille’s Press Release in its entirety

Richard Mile

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Huntington’s disease: brain abnormalities detectable as early as the embryonic stage https://institutducerveau-icm.org/en/actualite/huntingtons-disease-alters-human-neurodevelopment/ https://institutducerveau-icm.org/en/actualite/huntingtons-disease-alters-human-neurodevelopment/#respond Fri, 17 Jul 2020 13:15:14 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=19551 Although Huntington’s disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers For more information ]]> Although Huntington’s disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers suggest that Huntington’s disease might affect neurodevelopment. To determine whether this is actually the case, we examined tissue from human fetuses (13 weeks gestation) that carry the Huntington’s disease mutation. These tissues showed clear abnormalities in the developing cortex, including mislocalization of mutant huntingtin and junctional complex proteins, defects in neuroprogenitor cell polarity and differentiation, abnormal ciliogenesis, and changes in mitosis and cell cycle progression. We observed the same phenomena in Huntington’s disease mouse embryos, where we linked these abnormalities to defects in interkinetic nuclear migration of progenitor cells. Huntington’s disease thus has a neurodevelopmental component and is not solely a degenerative disease.

Sources :

Huntington disease alters human neurodevelopment

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A LARGE-SCALE EXPLORATION OF GENETIC FORMS OF PARKINSON’S DISEASE https://institutducerveau-icm.org/en/actualite/a-large-scale-exploration-of-genetic-forms-of-parkinsons-disease/ https://institutducerveau-icm.org/en/actualite/a-large-scale-exploration-of-genetic-forms-of-parkinsons-disease/#respond Mon, 06 Jul 2020 08:19:27 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19450 Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson's disease For more information ]]> Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson’s disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1587 cases. Mutations were found in 14.1% of patients: 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations.

 

Source :

Characterization of recessive Parkinson’s disease in a large multicenter study. Lesage S, et al. Ann Neurol. 2020 May 30.

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COVID-19: FIA FOUNDATION AND FIA SUPPORT THE BRAIN INSTITUTE https://institutducerveau-icm.org/en/actualite/covid-19-fia-foundation-and-fia-support-the-brain-institute/ https://institutducerveau-icm.org/en/actualite/covid-19-fia-foundation-and-fia-support-the-brain-institute/#respond Tue, 30 Jun 2020 12:18:17 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19429 LAUNCH OF AN UNPRECEDENTED STUDY TO FIND OUT THE IMPACT OF COVID-19 ON THE NERVOUS SYSTEM:

THE FIA FOUNDATION AND FIA PLEDGE SUPPORT FOR THE PARIS BRAIN For more information ]]> LAUNCH OF AN UNPRECEDENTED STUDY TO FIND OUT THE IMPACT OF COVID-19 ON THE NERVOUS SYSTEM:

THE FIA FOUNDATION AND FIA PLEDGE SUPPORT FOR THE PARIS BRAIN INSTITUTE

 

The Paris Brain Institute, in partnership with the AP-HP, Sorbonne-Université, Medico-University Department of Neurosciences at the Pitié-Salpêtrière Hospital, with grant of €400,000 from the FIA Foundation – historical patron of the Institute with a focus on public health – and support from FIA, is launching a major study to rapidly and accurately assess all the potential neurological and psychiatric impacts of Covid-19 on affected patients, with the aim of improving patient management, follow-up and rehabilitation.

 

Covid-19 is a multi-targeted viral disease whose disorders caused by the virus surprise by the diversity of symptoms, sometimes atypical. In addition to the lungs, many other organs can be affected by Covid-19 and lead to neurological complications such as loss of smell, loss of taste, headaches, dizziness, convulsions, stroke, altered consciousness and hemiplegia. In addition, the respiratory difficulties observed in patients with Covid-19 may be due to brain stem involvement in addition to the lungs. This region, located between the brain and the spinal cord, contains the centres that control breathing. However, experts know little about the overall impact of this coronavirus on the central nervous system, even though more than 10 million people worldwide are currently affected by the virus.

 

The data collected will be the subject of in-depth analysis, notably using artificial intelligence. The information obtained will be exploited in real time in order to draw practical consequences for patients as quickly as possible by May 2021.

 

 At the Paris Brain Institute, our mission is to find in order to cure. Therefore, the observations of our eminent specialists on this study will be decisive in helping people with Covid-19 to receive appropriate care. This ambitious project is led by the Neuroscience Medico-University Department at the Pitié-Salpêtrière hospital and the clinicians-researchers at the Paris Brain Institute, thanks to the FIA Foundation and the FIA, in favor of health for all. I would like to thank them very warmly. 

Gérard Saillant, President of the Paris Brain Institute and President of the FIA Medical Commission.

 The study will focus on:

– the neuropsychiatric manifestations of the affected individuals

– the psychiatric consequences for the patients themselves (due in particular to very long periods of resuscitation) as well as for their relatives

– the consequences for patients already suffering from neurological pathologies such as inflammatory diseases (including multiple sclerosis) and neurodegenerative diseases (such as Parkinson’s and Alzheimer’s). 

 

The long-term effects of the coronavirus on health are only beginning to be understood, so this important project will provide vital information to share with the world. We at the FIA Foundation are proud of our longstanding relationship with the Institute and its cutting-edge research.

Saul Billingsley, Executive Director of the FIA Foundation.

 

The Paris Brain Institute is probably one of the few centres in the world that is able to provide a comprehensive view of the neurology and psychiatry of Covid-19 infection. In the medium term, this will enable us as health professionals to be prepared to face a new pandemic and to have all the weapons at our disposal to better fight it. We can also think that this infection, when it strikes brains already damaged by a neurodegenerative or inflammatory disease, could have unknown effects. It is very important to know whether we are going to observe very atypical developments, for example in patients being monitored for Alzheimer’s disease or multiple sclerosis. There’s still a lot we don’t know. 

Prof. Jean-Yves Delattre, Medical Director of the Paris Brain Institute and Director of the AP-HP-Sorbonne University Neuroscience Medico-University Department at the Pitié-Salpêtrière Hospital, Prof. Jean-Christophe Corvol, Scientific Director of the project and Dr. Delorme, Principal Investigator.

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Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness https://institutducerveau-icm.org/en/actualite/two-new-fundamental-discoveries-for-the-diagnosis-and-treatment-of-patients-suffering-from-disorders-of-consciousness/ https://institutducerveau-icm.org/en/actualite/two-new-fundamental-discoveries-for-the-diagnosis-and-treatment-of-patients-suffering-from-disorders-of-consciousness/#respond Thu, 25 Jun 2020 13:57:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19401 Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness

The research team led by Prof. Lionel Naccache For more information ]]> Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness

The research team led by Prof. Lionel Naccache at the Paris Brain Institute (Sorbonne Université, APHP, INSERM, CNRS) has just published two important studies which concern patients suffering from a lasting disturbance of consciousness (e.g.: patients in ” vegetative state “or” minimally conscious state”). These two original studies correspond to part of the PhD work of Dr. Bertrand Hermann (INSERM, APHP, University of Paris) carried out under the supervision of Lionel Naccache.

 

A new clinical sign to probe the state of consciousness

The first work describes the discovery and validation of a new sign of clinical examination which makes it possible to identify among these non-communicating patients those whose brain function is the richest.  The researchers observed that the auditory startle reflex in response to noise (i.e.: blinking of the eyelids following a sudden sound) presented a habituation in patients capable of anticipating stimulus repetition. When the sounds were repeated, these patients were able to inhibit this behavioral response. Conversely, an inextinguishable startle response was present in patients whose detailed clinical examination and cerebral explorations (EEG with quantified high density, cognitive evoked potentials, diffusion tensor MRI, PET-scan with fluoro-deoxy- glucose) revealed very poor brain and cognitive activity. Beyond this precious diagnostic value, the presence of this clinical sign, – easy to find at patient’s bedside -, also made it possible to predict an improvement in their state of consciousness at six months. The invention of new clinical signs based on the use of the most recent structural and functional brain imaging techniques also demonstrates the contemporary vitality and renewal of neurological semiology. Published in the world’s largest neurology journal (Brain), this article was chosen by the editorial board as “Editor’s choice” because of its innovative nature and importance.

 

Reference : Hermann, B., A. Ben Salah, V. Perlbarg, M. Valente, N. Pyatigorskaia, M. O. Habert, F. Raimondo, J. Stender, D. Galanaud, A. Kas, L. Puybasset, P. Perez, S. J.D., B. Rohaut and L. Naccache (in press). “Habituation of auditory startle reflex is a new sign of minimally conscious state.” Brain

https://academic.oup.com/brain/article/doi/10.1093/brain/awaa159/5862031?searchresult=1

Improving consciousness with transcranial direct current stimulation of the prefrontal cortex

The second work reveals how transcranial direct current electrical stimulation (tDCS) of the frontal lobe can improve conscious state in some of these patients. By comparing patients who showed behavioral improvement after a single session of tDCS, to patients who did not show such an improvement, the researchers demonstrated that the clinical response to tDCS was associated with an increase in specific EEG markers of consciousness (long distance oscillations and communication between the prefrontal and parietal regions in the theta frequency band). The researchers also used a simulation model of the distribution of electric current based on the individual anatomy of the patients, to show that the clinical response to tDCS was correlated with the intensity of the electric field in the cortex next to the stimulation electrodes. These results are important both on the clinical level – by paving the way to the development of new therapeutic strategies for personalized patterns of tDCS stimulation – and on the level of basic research by confirming the importance of the prefrontal cortex and the fronto-parietal network in the physiology of consciousness, – as postulated by the theory of global neuronal space developed over the past twenty years by Stanislas Dehaene, Jean-Pierre Changeux and Lionel Naccache. This work was published in the journal Scientific Reports of the Nature group.

 

Reference : Hermann, B., Raimondo, F., Hirsch, L., Huang, Y., Denis-Valente M., Pérez P., Engemann, D., Faugeras, F., Weiss, N., Demeret, S., Rohaut, B., Parra, L.C., Sitt, J.D., Naccache, L. Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness. Sci Rep 10, 4323 (2020). https://doi.org/10.1038/s41598-020-61180-2

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APPLY NOW FOR THE IMIND – INTERNATIONAL MASTER IN NEURODEGENERATIVE DISEASES ! https://institutducerveau-icm.org/en/actualite/apply-now-for-the-imind-international-master-in-neurodegenerative-diseases/ https://institutducerveau-icm.org/en/actualite/apply-now-for-the-imind-international-master-in-neurodegenerative-diseases/#respond Wed, 03 Jun 2020 09:19:37 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19335 Interested in Neurosciences and neurodegeneratives diseases?

The application campaign for the iMIND - International Master in Neurodegenerative Diseases - Master 2 For more information ]]> Interested in Neurosciences and neurodegeneratives diseases?

The application campaign for the iMIND – International Master in Neurodegenerative Diseases – Master 2 program is now open! CLOSING DATE: JUNE 30, 2020.

iMIND is a selective programme built on the partnership between the Paris Brain Institute and Sorbonne University.

 

iMIND gathers expert researchers from the Paris Brain Institute and Neuroscience Paris Seine Institute, providing the students with an immersive experience in up-to-date innovative research topics in order to understand the functioning of the brain in normal and pathological conditions.

Details regarding iMIND can be found:

In the two following links:

Information regarding the application process are detailed here.

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MSCopilot, a new multiple sclerosis self-assessment digital solution, is clinically validated https://institutducerveau-icm.org/en/actualite/mscopilot-multiple-sclerosis-digital-solution/ https://institutducerveau-icm.org/en/actualite/mscopilot-multiple-sclerosis-digital-solution/#respond Tue, 02 Jun 2020 13:40:36 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18544 MSCopilot, a new multiple sclerosis self-assessment digital solution developed by AdScientiam a startup incubated at iPEPS, has been clinically validated in a For more information ]]> MSCopilot, a new multiple sclerosis self-assessment digital solution developed by AdScientiam a startup incubated at iPEPS, has been clinically validated in a clinical trial involving several French hospitals. The results are published in the European Journal of Neurology.

Assessing patients’ disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC).

This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores.

In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot.

This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.

The MSCopilot application has been presented to neurologists through a video that you can discover below:

 

 

Source

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

Maillart E, Labauge P, Cohen M, Maarouf A, Vukusic S, Donzé C, Gallien P, De Sèze J, Bourre B, Moreau T, Louapre C, Mayran P, Bieuvelet S, Vallée M, Bertillot F, Klaeylé L, Argoud AL, Zinaï S, Tourbah A. Eur J Neurol. 2019 Sep 20.

 

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Schizophrenia, a myelin deficiency ? https://institutducerveau-icm.org/en/actualite/schizophrenia-a-myelin-deficiency/ https://institutducerveau-icm.org/en/actualite/schizophrenia-a-myelin-deficiency/#respond Thu, 14 May 2020 09:45:10 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19139 Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia, NATURE COMMUNICATIONS.

Dorien MAAS, PhD and Brahim For more information ]]> Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia, NATURE COMMUNICATIONS.

Dorien MAAS, PhD and Brahim NAIT-OUMESMAR, co-team leader at the Paris Brain Institute, just published in Nature Communications on the prefrontal cortex myelination as a key feature in schizophrenia aetiology.

 

Abstract

Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.

 

Source :

Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia , NATURE COMMUNICATIONS volume 11, Article number: 2329 (2020)

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ACTIVATION OF THE INNATE IMMUNE SYSTEM IN THE CENTRAL NERVOUS SYSTEM, A MARKER FOR THE DEVELOPMENT OF DISABILITY IN MULTIPLE SCLEROSIS? https://institutducerveau-icm.org/en/actualite/activation-of-the-innate-immune-system-in-the-central-nervous-system-a-marker-for-the-development-of-disability-in-multiple-sclerosis/ https://institutducerveau-icm.org/en/actualite/activation-of-the-innate-immune-system-in-the-central-nervous-system-a-marker-for-the-development-of-disability-in-multiple-sclerosis/#respond Wed, 06 May 2020 09:14:05 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18817

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) For more information ]]>

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS).

Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and 18F-DPA-714 PET. A threshold of significant activation of 18F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as “DPA-active”, “DPA-inactive” or “unclassified”.

Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS.

Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.

 

Source

Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of disability worsening in Multiple Sclerosis. Bodini B, et al. J Nucl Med 2020.

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Mechanisms and therapeutic implications of hypermutation in gliomas https://institutducerveau-icm.org/en/actualite/mechanisms-and-therapeutic-implications-of-hypermutation-in-gliomas/ https://institutducerveau-icm.org/en/actualite/mechanisms-and-therapeutic-implications-of-hypermutation-in-gliomas/#respond Tue, 28 Apr 2020 15:24:44 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18874 A high tumour mutational burden (hypermutation) is observed in some gliomas1,2,3,4,5; however, the mechanisms by which hypermutation develops and whether it predicts For more information ]]> A high tumour mutational burden (hypermutation) is observed in some gliomas1,2,3,4,5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood.

Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide.

Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade.

Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations.

These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer.

 

Source :

Mechanisms and therapeutic implications of hypermutation in gliomas, Nature 2020.

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Four core properties of the human brain valuation system demonstrated in intracranial signals https://institutducerveau-icm.org/en/actualite/four-core-properties-of-the-human-brain-valuation-system-demonstrated-in-intracranial-signals/ https://institutducerveau-icm.org/en/actualite/four-core-properties-of-the-human-brain-valuation-system-demonstrated-in-intracranial-signals/#respond Thu, 16 Apr 2020 15:05:35 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18844 Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies For more information ]]> Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies have identified brain regions, such as the ventromedial prefrontal cortex (vmPFC) and lateral orbitofrontal cortex (lOFC), composing a value system.

In the present study, in an effort to bridge across species and techniques, we investigated the neural representation of value ratings in 36 people with epilepsy, using intracranial electroencephalography.

We found that subjective value was positively reflected in both vmPFC and lOFC high-frequency activity, plus several other brain regions, including the hippocampus. We then demonstrated that subjective value could be decoded (1) in pre-stimulus activity, (2) for various categories of items, (3) even during a distractive task and (4) as both linear and quadratic signals (encoding both value and confidence). Thus, our findings specify key functional properties of neural value signals (anticipation, generality, automaticity, quadraticity), which might provide insights into human irrational choice behaviors.

 

Source

Four core properties of the human brain valuation system demonstrated in intracranial signals, Nature Neurosciences 2020.

 

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Covid-19 pandemic: Paris Brain Institute mobilizes and carries on https://institutducerveau-icm.org/en/actualite/covid-19-pandemic-paris-brain-institute-mobilizes-and-carries-on/ https://institutducerveau-icm.org/en/actualite/covid-19-pandemic-paris-brain-institute-mobilizes-and-carries-on/#respond Sat, 21 Mar 2020 07:00:46 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18793 In the context of the coronavirus pandemic, the Paris Brain Institute pursues its research activity in the best way possible and participates actively in the effort For more information ]]> In the context of the coronavirus pandemic, the Paris Brain Institute pursues its research activity in the best way possible and participates actively in the effort to fight the virus and help patients.

The Covid-19 pandemic has disrupted our activities and put on hold our lab-based work to a significant extent. All research teams have reduced their experiments to the minimum necessary, focusing on bringing their ongoing experiments to a successful conclusion. Almost all our staff now work from home and pursue their activities in the best way possible under the circumstances, analyzing data, writing papers and grants, and using virtual tools to communicate with one another. Research never stops!

Located in the heart of the Pitié-Salpêtrière Hospital, which receives many Covid-19 patients, the Paris Brain Institute is in close contact with the medical teams and has already offered access to its equipment and skills to participate in the screening and care of patients.

Furthermore, all our clinicians who are members of both the Paris Brain Institute and the Neuroscience Medico-University department of the hospital are mobilized to support the medical teams taking care of Covid-19 patients, as Pitié-Salpêtrière is now the reference center for the Covid-19 patient care.

In these difficult times, we need to reaffirm our values:

– For communication based on scientific and medical research facts, especially in the context of much fake news and false information being spread all over the internet.

– At the service of patients and knowledge, always.

– Openness and collaboration are the key to progress and we do our best to offer as much help as possible to the teams fighting the virus.

We cannot predict how the situation will evolve over coming weeks and months, but we are confident that the efforts of the physicians, nurses and all healthcare and research professionals involved will prevail. Our thoughts go out to all, and in particular to those for whom this crisis is adding to the burden of an affected brain. When the dust settles on this pandemic, the millions who suffer from disorders of the brain and mind will still need us. I can assure you that the Paris Brain Institute will be there to pursue its commitment to understand the brain and its pathologies, at the service of patients and the public.

Sincerely,

Prof Alexis Brice, Executive Director

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Emergence of behavioral individuality in the fly’s brain https://institutducerveau-icm.org/en/actualite/emergence-of-behavioral-individuality/ https://institutducerveau-icm.org/en/actualite/emergence-of-behavioral-individuality/#respond Fri, 20 Mar 2020 08:59:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18755  Where does our individuality come from? What makes us unique in our behavior? Could it all be in our brain? Prof. Bassem Hassan* and his team discovered a For more information ]]>  Where does our individuality come from? What makes us unique in our behavior? Could it all be in our brain? Prof. Bassem Hassan* and his team discovered a stochastic wiring mechanism of circuits in the fly’s brain at the origin of individual behavior, which might represent a general principle of how certain aspects of individuality emerge in the brain. Results are published in Science.

 

 The idea that brain circuits regulate behavior is pretty straightforward notion. If a circuit is different between individuals, then it might influence their behavior individually. This could explain some of the behavioral idiosyncrasy present in population. But how to demonstrate this idea in an experimental setting?

 

“The first problem we had to tackle was: how do you find a behavior that corresponds to the wiring of these particular neurons?” explains Prof Bassem Hassan. “The breakthrough came when a colleague of mine, Andrew Straw, contacted me, to tell me that while he was studying a specific behavior, he found that the specific circuit we were studying regulated that behavior. This is when the adventure took a leap” explains Bassem Hassan

 

Bassem Hassan and his team have been working on this specific circuit of the brain, a visual system circuit called Dorsal Cluster Neurons (DCN) for several years. They had identified a stochastic anatomical and developmental variability in this system meaning that the brain of one fly develop slightly differently from the brain of another fly and as soon as the development is finished, that pattern is stable throughout the fly’s life.

But what about behavior? Is it as stable and unique as the circuit? To delve that question, the team started to test this behavior in flies for several weeks checking and showed this behavior remained constant in an individual fly but differed between flies. Moreover, they observed that with every generation the entire variance of the behavior was reset, meaning that the behavioral individuality was more the result of the unique development of each brain, than the specific genome of each individual.

 

“Now we had the behavior and the circuit, both unique to an individual fly and stable over time, but what is the link between the two?”

 

To explore this question, they conducted a series of experiments, led by Dr. Gerit Linneweber the first author of the study, in close collaboration with the team of Prof. Peter Robin Hiesinger in Berlin. By modifying the wiring in the flies’ brain and silencing DCN, an expertise they gathered from more than 10 years working on that circuit, they showed that the strongest anatomical correlate was left-right asymmetry in the wiring of a specific area that correlate with narrow or wide a path a fly would take toward an object. Not only that, but also a causal link between the circuit and behavior when rewiring the circuit happened to shift the flies’ behavior while maintaining the correlation between the circuit and the behavior in individual flies. These results established that the way the circuit develops causally underlies to a certain significant extent, the way the animal behaves.

 

“The idea that there is something innate about certain aspects of idiosyncrasy, that we would call “personality” in human psychology, and that it originates in the brain, is a very old idea. For the first time we can pinpoint to a clear distinctive brain-based origin for a parameter of what we could call an animal’s personality. The fact that it is due to developmental mechanisms that cannot be predicted either by the environment alone or the genome alone but from the phenomenon of stochastic developmental noise is super exciting. We are lucky enough to begin to solve two mysteries at the same time.

Doing this very basic research for a long time, which had no other obvious goal than understanding how the brain develops, and being able to show that by taking those approach and slowly building a knowledge base about a certain question you are interested in simply by curiosity-driven science, is extremely satisfying and a real reward for the effort of so many people in the team.” Concludes Bassem Hassan


*Bassem Hassan is scientific director and team leader at Paris Brain Institute, Allen Distinguished Investigator and “Einstein Visiting Fellow” of the Berlin Institute of Health at the Free University of Berlin.

 

Source

A neurodevelopmental origin of behavioral individuality in the Drosophila visual system.Linneweber GA et al, Science. March 2020.

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TOURETTE SYNDROME : MOTOR IMPULSES DO NOT PREDICT PATIENTS’ TICS https://institutducerveau-icm.org/en/actualite/tourette-syndrome-motor-impulses-do-not-predict-patients-tics/ https://institutducerveau-icm.org/en/actualite/tourette-syndrome-motor-impulses-do-not-predict-patients-tics/#respond Fri, 20 Mar 2020 07:53:32 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18745 CYRIL ATKINSON-CLÉMENT (Institut du Cerveau - ICM) AND YULIA WORBE (SORBONNE UNIVERSITÉ/APHP) IN THE TEAM “NORMAL AND ABNORMAL MOTOR CONTROL: MOVEMENT DISORDERS For more information ]]> CYRIL ATKINSON-CLÉMENT (Institut du Cerveau – ICM) AND YULIA WORBE (SORBONNE UNIVERSITÉ/APHP) IN THE TEAM “NORMAL AND ABNORMAL MOTOR CONTROL: MOVEMENT DISORDERS AND EXPERIMENTAL THERAPEUTICS” AT PARIS BRAIN INSTITUTE, SHOW THAT THE CONTROL OF MOTOR IMPULSIVITY, THE TRAIT THAT CHARACTERIZES THE ABILITY TO INHIBIT A MOVEMENT OR ACTION ALREADY STARTED, IS NOT CORRELATED WITH TICS IN PATIENTS WITH TOURETTE’S GILLES SYNDROME. THESE RESULTS, PUBLISHED IN THE JOURNAL CORTEX, SHED NEW LIGHT ON THIS COMPLEX PATHOLOGY.

 

Abnormality of inhibitory control is considered to be a potential cognitive marker of tics in Tourette disorder (TD), attention deficit hyperactivity disorder (ADHD), and impulse control disorders. The results of the studies on inhibitory control in TD showed discrepant results. The aim of the present study was to assess reactive inhibitory control in adult TD patients with and without antipsychotic medication, and under emotional stimulation (visual images with positive, neutral and negative content).

 

We assessed 31 unmedicated and 19 medicated TD patients and 26 matched healthy controls using the stop signal task as an index of reactive motor impulsivity and emotional stimulation with the aim to increase impulsivity. We performed a multimodal neuroimaging analysis using a regions of interest approach on grey matter signal, resting-state spontaneous brain activity and functional connectivity analyses.

 

We found a higher reactive motor impulsivity in TD patients medicated with antipsychotics compared to unmedicated TD patients and controls. This propensity for reactive motor impulsivity in medicated TD patients was not influenced by ADHD or emotional stimulation. Neuroimaging results in medicated TD patients suggested that reactive motor impulsivity was underpinned by an increased grey matter signal from the right supplementary motor area and inferior frontal gyrus; decreased resting-state spontaneous activity of the left putamen; higher functional connectivity between the inferior frontal gyrus and the superior temporal gyri (bilaterally); lower functional connectivity between the cerebellum and the right subthalamic nucleus.

 

Taken together, our data suggested (i) a deficit in reactive motor impulsivity in TD patients medicated with atypical antipsychotics that was unrelated to ADHD and (ii) that motor impulsivity was underpinned by structures and by functional connectivity of the fronto-temporo-basal ganglia-cerebellar pathway.

 

Source

Neural correlates and role of medication in reactive motor impulsivity in Tourette disorder.

Atkinson-Clement C, et al. Cortex 2019.

 

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Scipio bioscience raises €6.0 M Series A financing  https://institutducerveau-icm.org/en/actualite/scipio-bioscience-raises-e6-0-m-series-a-financing/ https://institutducerveau-icm.org/en/actualite/scipio-bioscience-raises-e6-0-m-series-a-financing/#respond Fri, 20 Mar 2020 07:10:48 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18702 To develop and launch a kit dedicated to sample preparation for single-cell RNA-sequencing 

Paris, 25 February 2020 - Scipio bioscience, a Paris-based biotechnology For more information ]]> To develop and launch a kit dedicated to sample preparation for single-cell RNA-sequencing 

Paris, 25 February 2020 – Scipio bioscience, a Paris-based biotechnology company, developing a new generation of single-cell sequencing solutions, announces today that it has secured a €6.0 M Series A financing from an international syndicate led by M Ventures (Amsterdam, The Netherlands), the corporate venture capital arm of Merck. The initial shareholders Seventure Partners’ Quadrivum I (Paris, France) and High-Tech Gründerfonds (Bonn, Germany) participated in the capital increase, alongside additional investors Financière Arbevel (Paris, France) and investiere (Zürich, Switzerland). 

There is a substantial unmet need for cost-effective single-cell sequencing methods. The availability of such methods will drive single-cell market growth globally, both in the basic and clinical research fields. Scipio bioscience is pioneering affordable single-cell sample preparation for sequencing. We fully support the team to deliver a much-needed solution based on their disruptive technology and to grow Scipio bioscience into a major player in single-cell biology” says Arnaud Autret, Investment Principal at M Ventures. 

Philippe Tramoy, Partner at the Quadrivium 1 seed capital fund at Seventure Partners, adds: “We are thrilled that our seed investment in Scipio’s truly deep tech project was crucial to turn its disruptive technology into a potential game changer. We look forward to getting to the next phases of development.  

Prof Stuart Edelstein, President, says: “We are convinced that our user-friendly kit, requiring no specific equipment and accessible for any benchtop, will enable thousands of additional scientists to perform single-cell RNA-sequencing. This availability will change the way biological questions are addressed and ultimately benefit both basic research and clinical applications. We are delighted to initiate collaborations for beta-testing of our kit, initially with Institut du Cerveau – ICM (Brain & Spine Institute, Paris, France) laboratories, as the interactions so far with its world-class teams and cutting-edge core facilities have been extremely fruitful. Our goal is to extend collaborations to leading European research institutes.” 

The €6.0 M Series A funding will fuel the final development of its single-cell RNA-sequencing kit, as well as marketing and business development efforts to prepare for commercial launch in 2022. 

About Scipio bioscience 

Scipio bioscience develops a new generation of single-cell sequencing solutions, to answer the growing needs of clinical and basic research labs. The patented technology is based on an innovative chemical approach conceived by its President and Co-Founder, Prof Stuart Edelstein, a world-renowned biophysicist. Pierre Walrafen, PhD, CEO and Co-Founder of Scipio Bioscience, directs a team composed of scientists with expertise in molecular biology, chemistry, and bioinformatics. The company, hosted in the iPEPS-Institut du Cerveau – ICM incubator of the Brain & Spine Institute (Institut du Cerveau – ICM, Pitié-Salpêtrière Hospital, Paris), has developed the protocol from the initial proof-of-concept studies to a prototype kit ready for beta-testing by collaborating research teams. Scipio bioscience was supported by a grant from the Région Île-de-France and the Programme d’Investissement d’Avenir, operated by BPI France. 

For more information: www.scipio.bio 

About M Ventures 

M Ventures is the strategic, corporate venture capital arm of Merck. Its mandate is to invest in innovative technologies and products with the potential to significantly impact the company’s core business areas. From its headquarters in Amsterdam and offices in the US and Israel, M Ventures invests globally in transformational ideas driven by great entrepreneurs. M Ventures takes an active role in its portfolio companies and teams up with entrepreneurs and co-investors to translate innovation towards commercial success. For more information, visit www.m-ventures.com 

About Quadrivium 1 Seed Fund 

The Quadrivium 1 Seed Fund is one of the venture funds managed by Seventure Partners. This fund finances French companies in the seed round (FNA – Future Investment Program) in the areas of Life Sciences & Digital Technologies, which are related to or linked to the academic cluster federated around the UPMC, Paris II University, Paris IV University, National Museum of Natural History, IRCAM, ENSCI, Technological University of Compiègne, CNRS, Curie Institute , Pierre Gilles de Gennes Foundation, Voir et Entendre Foundation and Paris Sciences et Lettres (PSL). 

About Seventure Partners 

With €750 M net commitments under management as of the end of 2018, Seventure Partners is a leading venture capital firm in Europe. Since 1997, Seventure Partners has been investing in innovative businesses with high growth potential in two fields: Life sciences across Europe, Israel, Asia and North America and Digital technologies in France and Germany. Investments can range between €500 k and €10 M per round, or up to €20 M per company, from early to late stage. Seventure Partners is a subsidiary of Natixis Investment Managers. Natixis is a subsidiary of Groupe BPCE, the second-largest banking group in France. 

For more details: www.seventure.fr/en Twitter: @seventurep 

About the High-Tech Gründerfonds 

High-Tech Gründerfonds (HTGF) is a seed investor that finances high-potential, tech-driven start-ups. With €895.5 M in total investment volume across three funds and an international network of partners, HTGF has already helped forge more than 560 start-ups since 2005. Driven by their expertise, entrepreneurial spirit and passion, its team of experienced investment managers and start-up experts help guide the development of young companies. HTGF’s focus is on high-tech start-ups in a range of sectors, including software, hardware and life sciences/ chemistry. To date, external investors have injected over €2 B into the HTGF portfolio via about 1,400 follow-on financing rounds. HTGF has also successfully sold interests in more than 100 companies. 

Investors in the public-private partnership include the German Federal Ministry of Economics and Energy, KfW Capital, the Fraunhofer-Gesellschaft and the commercial enterprises ALTANA, BASF, Bayer, Boehringer Ingelheim, B. Braun, Robert Bosch, BÜFA, CEWE, Deutsche Post DHL, Dräger, Drillisch AG, EVONIK, EWE AG, FOND OF, Haniel, Hettich, Knauf, Körber, LANXESS, media + more venture Beteiligungs GmbH & Co. KG, PHOENIX CONTACT, Postbank, QIAGEN, RWE Generation SE, SAP, Schufa, Schwarz Gruppe, STIHL, Thüga, Vector Informatik, WACKER and Wilh. Werhahn KG. 

About Financière Arbevel 

Founded in 1997, Financière Arbevel, an entrepreneurial investment management company, has grown significantly since its takeover by the current owners in early 2009 – the AUM progressed from €25 M to €1.9 B as of today (of which €752 M under the umbrella SICAV “Pluvalca” comprising 9 sub-funds). The company currently employs a total of 34 staff, of which 13 are dedicated to fund management/investment research. Financière Arbevel is recognized for its expertise within the small & mid cap asset class. We are a research-driven organization with a strong emphasis on fundamental financial and strategic analysis, close relationships with top managements of listed companies (more than 1,000 company meetings last year) and a permanent quest for new investment themes offering structural growth opportunities. The digitalization, fintech, Industry 4.0, or the ageing of the world population are some of our favorite investment themes. We ensure we are following closely the latest developments within this universe, by participating in various conferences, trade fairs, sector-specific thematic events and by meeting regularly with managements of listed companies. Our small & mid cap DNA is spread across various strategies under the PLUVALCA family of funds with a cross-asset approach comprising our core equity funds, thematic equity funds, fixed income and diversified/flexible allocation funds). In 2015, the Norwegian sovereign wealth fund chose Financière Arbevel to manage its French equity mandate. In 2018, Financière Arbevel pursued its development by launching its first European private equity fund (FPCI form or “Professional private equity investment fund”) with a cross-over approach focused on the non-listed life-science universe, with the idea of accompanying a limited number of biotechnology start-ups in their development. www.arbevel.com 

About investiere 

investiere is the leading European startup investment platform for qualified and institutional investors. A team of investment professionals screens thousands of companies and presents the best investment opportunities on a digital platform after a rigorous due diligence process. investiere focuses on European high-tech startups. The investiere community consists of more than 4,000 qualified private investors, family offices and pension funds. Furthermore, numerous corporations rely on investiere’s expertise to screen, select and invest in promising startups. With CHF 100 M invested since inception in 2010, investiere is Switzerland’s most active startup investor. Switzerland’s third-largest bank, Zürcher Kantonalbank, is an anchor investor of investiere. To join investiere’s growing international investor community, visit www.investiere.ch. 

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THE FIRST COMPLETE MAPPING OF CEREBRAL VASCULATURE https://institutducerveau-icm.org/en/actualite/the-first-complete-mapping-of-cerebral-vasculature/ https://institutducerveau-icm.org/en/actualite/the-first-complete-mapping-of-cerebral-vasculature/#respond Fri, 14 Feb 2020 12:26:22 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18644 Paris, February 13, 2020 – The team of Nicolas Renier at the Paris Brain Institute has succeeded in reconstructing the entire cerebral vascular system of mice with For more information ]]> Paris, February 13, 2020 – The team of Nicolas Renier at the Paris Brain Institute has succeeded in reconstructing the entire cerebral vascular system of mice with unprecedented precision. This work has been conducted in collaboration with Christoph Kirst, now assistant professor at UCSF, California. While many neurological and psychiatric pathologies have a vascular component, it is still under-studied due to the complexity of the blood vessels’ network, intimately intertwined with neural cells. The tool developed by the researchers opens the way to important research on the role of cerebral vascularization in the evolution of many brain diseases. The results of this study are published in the journal Cell.

 

To meet its important needs for oxygen and nutrients, the brain is very richly vascularized in blood veins, arteries and capillaries. The cerebral vascular system plays an essential role in the function and maintenance of neuronal circuits. Many brain pathologies, both neurodegenerative and neuropsychiatric (schizophrenia, autism or depression), have a vascular component which, although not necessarily the cause of these diseases, can be an aggravating factor. The study of the cerebral vascular system as a whole represents a major challenge, due to its density and complexity, but also an opportunity because its complete 3D reconstruction is now possible.

 

Mission accomplished for Nicolas Renier’s team at the Paris Brain Institute. Thanks to a combination of expertise in mathematics (Christoph Kirst and Sophie Skriabine) and neurobiology (Alba Vieites-Prado and Thomas Topilko), the researchers have succeeded in reconstructing the entire cerebral vascular system of the mouse at very high resolution with automatic recognition of the nature of each vessel (artery, capillary or vein). Since the conclusion of this study, several dozen brains have been reconstructed, as the technique makes it faster and easier to obtain this data. Whereas such reconstructions used to take several months or years of manual work per brain before, researchers can now reconstruct a brain in just 2 days.

 

To accomplish this, they have developed a bio-marking method to distinguish blood arteries, veins and capillaries in an optically transparent brain in order to record three-dimensional images using the latest imaging technique, light sheet microscopy. These highly complex raw data of the cerebral vasculature then passed into the hands of mathematicians who developed a software to reconstruct these images using innovative approaches combining formal mathematics and artificial neural networks.

 

Detail of an automated reconstruction of a cerebral vascular network, at the level of the hippocampus, showing arteries in red, veins in blue, cortical capillaries in dark green, hippocampal capillaries in light green, and finally thalamic capillaries in pink.

Detail of an automated reconstruction of a cerebral vascular network, at the level of the hippocampus, showing arteries in red, veins in blue, cortical capillaries in dark green, hippocampal capillaries in light green, and finally thalamic capillaries in pink.

 

The result is a three-dimensional mathematical reconstruction of the cerebral vascular system, distinguishing the different types of blood vessels, their location and organization in the different brain regions. On the scale of a mouse brain (about 1cm3), this represents almost 280 meters and some 8 million vessels with major regional variations in terms of vessel density, very important in the sensory regions for example.

 

“These reconstructions open the way to new working hypotheses and opportunities, particularly to study the alteration to the vascular network in different pathologies, but also to understand the intimate organization of the cerebrovascular network and how it supports neuronal functions. “explains Nicolas Renier

 

To validate this methodology, the research team collaborated with Piotr Topilko’s team, which is developing experimental models of stroke, to study the impact of a stroke, which corresponds to the obstruction or rupture of a cerebral artery, on the brain’s vasculature. They observed a massive redirection of blood capillaries to the site of the stroke. “The vascular network, even in an adult brain, is extremely plastic and can be subject to very significant changes.” continues Nicolas Renier.

 

Having shown that the sensory regions were among the most densely vascularized in the brain, the researchers, in collaboration with Nicolas Michalski and Christine Petit of the Institut Pasteur, studied the effect of deafness on the cerebral vascular network.  They were able to measure that during congenital deafness, the vascularization of the auditory areas is largely diminished in favor of an increase in the vascularization of the cerebral areas associated with touch and sight. A form of compensation would thus exist between the different cerebral areas, the neuronal communication between these areas influencing the reorganization of the vascular network.

 

“These data are very encouraging and drive us to explore other pathological contexts in which neuronal activity is affected. The tool we have developed allows us to perform these reconstructions on a whole-brain scale in different contexts and thus generate new hypotheses on how various diseases modify vascular topology. “concludes Nicolas Renier.

 

Source

 

Mapping the fine scale organization and plasticity of the brain vasculature, Christoph Kirst, Sophie Skriabine, Alba Vieites-Prado, Thomas Topilko, Paul Bertin, Gaspard Gerschenfeld, Florine Verny, Piotr Topilko, Nicolas Michalski, Marc Tessier-Lavigne, Nicolas Renier, Cell, February 2020.
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6 ICM researchers awarded the prestigious European fellowship Marie Sklodowska-Curie Actions https://institutducerveau-icm.org/en/actualite/6-icm-researchers-awarded-the-prestigious-european-fellowship-marie-sklodowska-curie-actions/ https://institutducerveau-icm.org/en/actualite/6-icm-researchers-awarded-the-prestigious-european-fellowship-marie-sklodowska-curie-actions/#respond Thu, 06 Feb 2020 15:13:46 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18628 This year, 6 young Institut du Cerveau - ICM researchers were awarded a Marie Sklodowska-Curie Actions postdoctoral fellowship. A record!

 

The Marie For more information ]]> This year, 6 young Institut du Cerveau – ICM researchers were awarded a Marie Sklodowska-Curie Actions postdoctoral fellowship. A record!

 

The Marie Sklodowska-Curie Actions (MSCA) fellowships are part of Horizon 2020, the EU’s framework programme for research and innovation. They are awarded to outstanding post-doctoral researchers and outstanding doctoral and post-doctoral training programmes.

This year, among the 1500 European winners, 6 are Institut du Cerveau – ICM researchers! This is a record since the Institute’s creation. This result demonstrates the excellence of the research conducted at the Institut du Cerveau – ICM and of the researchers recruited.

The 6 Institut du Cerveau – ICM laureates are:

– Adrien Martel

– Yannick Mullié

– Martina Bracco

– Yann Le Guen

– Yann Zerlaut

– Yonatan Sanz-Perl

 

“Congratulations to the six laureates! We are very proud of this result and of all these excellent young researchers who conduct cutting-edge research in neuroscience at the Institut du Cerveau – ICM. “Alexis Brice, Executive Director of the Institut du Cerveau – ICM

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BASSEM HASSAN RECEIVES THE PRESTIGIOUS  ROGER DE SPOELBERCH PRIZE 2019  https://institutducerveau-icm.org/en/actualite/bassem-hassan-receives-the-prestigious-roger-de-spoelberch-prize-2019/ https://institutducerveau-icm.org/en/actualite/bassem-hassan-receives-the-prestigious-roger-de-spoelberch-prize-2019/#respond Thu, 06 Feb 2020 13:41:40 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18621  

Paris, February 5th 2020 - Bassem Hassan, head of the "Brain Development" team and Scientific Director of the Brain and Spinal Cord Institute (Institut du Cerveau For more information ]]>  

Paris, February 5th 2020 – Bassem Hassan, head of the “Brain Development” team and Scientific Director of the Brain and Spinal Cord Institute (Institut du Cerveau – ICM), received the Roger de Spoelberch Prize for his research project in the field of neurodegenerative diseases. 

Each year, the Geneva-based Roger de Spoelberch Foundation awards its prize to a clinical and fundamental scientific research project in the field of neurodegenerative and psychiatric diseases. 

This year, Bassem Hassan, head of the “Brain Development” team and Scientific Director of the Institut du Cerveau – ICM, received the Roger de Spoelberch 2019 prize for his project entitled “The Amyloid Precursor Protein in neuronal development, homeostasis and demise”. 

My lab is interested in asking fundamental questions about how the brain develops and maintains its health throughout life. We think neurodegenerative disease is actually caused by a failure of pro-health mechanisms, rather than the onset of toxic mechanisms. The Amyloid Precursors Protein is very well known and widely studied for its involvement in Alzheimer’s disease, but what it does in a normal brain is – surprisingly – still unclear. There is a lot of evidence to suggest that this protein, which is very conserved in evolution and expressed throughout the brain, may be part of what keeps the brain healthy throughout life. The project is about exploring how exactly this protein contributes to healthy brain development and ageing. The hope is that this knowledge will spur new discoveries so that physicians might one day be able to exploit normal health mechanisms to ameliorate the lives of people who suffer from brain disorders.” Bassem Hassan 

The aim of the Roger de Spoelberch Foundation is to encourage scientific and medical research to develop new ways of combating neurodegenerative diseases and certain psychiatric illnesses that seriously alter behavior such as schizophrenia. The Roger de Spoelberch Award represents significant financial support for the continuation of this project in Alzheimer’s disease to better understand the role of this protein in neuronal function. 

I am very grateful to the Roger De Spoelberch Foundation for supporting this line of research. It shows that the foundation is not afraid to believe and invest in new ideas, and we need more of that in science. I am also humbled by the prize which recognizes our past achievements. Some of the world’s most renowned neuroscientists have won this prize in the past and I feel very privileged to be among such esteemed colleagues. I am also very proud of Institut du Cerveau – ICM, because we are now the only institute which has had two winners of this prestigious prize, and that shows that Institut du Cerveau – ICM is a place for high quality brain research  

The award ceremony will take place on March 17 at 10 a.m. at the Brain and Spinal Cord Institute. 

More information on the Roger Spoelberch Foundation

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THE CHARCOT LIBRARY, A SHOWCASE OF KNOWLEDGE https://institutducerveau-icm.org/en/actualite/charcot-library/ https://institutducerveau-icm.org/en/actualite/charcot-library/#respond Tue, 04 Feb 2020 09:18:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18545 On the occasion of the Institut du Cerveau - ICM’s 10th anniversary, FOCUS on the Charcot Library !!!

The Institut du Cerveau - ICM has a historical legacy, For more information ]]> On the occasion of the Institut du Cerveau – ICM’s 10th anniversary, FOCUS on the Charcot Library !!!

The Institut du Cerveau – ICM has a historical legacy, illustrated by the presence within its walls of the Charcot Library (Sorbonne Université). It is named after Jean-Martin Charcot (1825-1893), a famous French neurologist and academician, considered the father of clinical neurology and founder, in 1880, of the Archives de neurologie(Neurology Archives).

The library contains 5000 volumes, hundreds of thesis compiled by Charcot in dummy collections, but also dozens of journals in French, English, German, and Italian.

In this library you will find the development of French medical literature in neurology. This library also abounds with many other medical, scientific, psychological and even religious subjects.

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Core facilities R&D #1: A cutting-edge R package for MEG-EEG statistical analysis https://institutducerveau-icm.org/en/actualite/meg-eeg-statistical-analysis/ https://institutducerveau-icm.org/en/actualite/meg-eeg-statistical-analysis/#respond Wed, 22 Jan 2020 12:36:11 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18507 Because the quality of scientific discoveries depends very strongly on the match between research projects and the evolution of technology, the Institut du Cerveau - For more information ]]> Because the quality of scientific discoveries depends very strongly on the match between research projects and the evolution of technology, the Institut du Cerveau – ICM offers you, in this new series of articles, to discover the work carried out by its core facilities to constantly adapt to technological advances and the requirements induced by scientific research. First stop at the Magnetoencephalography and Electroencephalography (MEG-EEG) core facility and its cutting-edge R package for MEG-EEG statistical analysis, carried by Lydia YAHIA CHERIF, research engineer on the MEG-EEG core facility & Ivan MOSZER, operational manager of the Institut du Cerveau – ICM bioinformatics and biostatistics core facility, iCONICS. 

The MEG-EEG center provides infrastructure and computing tools as well as technical and scientific support to researchers for data acquisition and analysis.

The growing complexity of neuroscience research results in elaborate experimental designs with multimodal recordings. MEG-EEG experiments are increasingly integrating MRI, physiological parameters (heart, skin and motion), neuropsychological results (tests scores) and behavioral data. Moreover, mixed designs with unequal sample sizes, multiple variables vs. insufficient observations are more and more frequent.

Conventional techniques such as standard repeated measures ANOVA with a simple variance-covariance matrix are unable to handle such situations. Advanced techniques are thus required, such as random and fixed effects GLM, linear mixed effect models, PLS techniques. Except for SPM, which is dedicated to MRI analysis, t-test with multiple comparisons correction is most often the unique test provided by the existing toolboxes for MEG-EEG data analysis.

There is a pressing need for a software solution that integrates methods for multivariate statistical analysis of electro-physiological data, and proposes advanced and innovative techniques adapted to MEG-EEG recording structure and experimental designs.

Therefore, Lydia YAHIA CHERIF and Ivan MOSZER are currently developing an R package dedicated to statistical analysis of MEG-EEG data, which integrates state of the art methods adapted to MEG-EEG data structure. This R package will be the first one dedicated to MEG-EEG statistical analysis. As an R package, it will be open to external contributions and will be enhanced and maintained in the long term. Given the evident lack of statistical tools for MEG-EEG signals, this package will be most probably highly welcomed by the international community.

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Modulation of Coordinated Activity across Cortical Layers by Plasticity of Inhibitory Synapses https://institutducerveau-icm.org/en/actualite/modulation-of-coordinated-activity-across-cortical-layers-by-plasticity-of-inhibitory-synapses/ https://institutducerveau-icm.org/en/actualite/modulation-of-coordinated-activity-across-cortical-layers-by-plasticity-of-inhibitory-synapses/#respond Wed, 22 Jan 2020 11:14:59 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18504 In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the For more information ]]> In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicits strong feedforward inhibition (FFI) onto L5 PNs. We find that FFI involving parvalbumin (PV)-expressing cells is strongly potentiated by postsynaptic PN burst firing. FFI plasticity modifies the PN excitation-to-inhibition (E/I) ratio, strongly modulates PN gain, and alters information transfer across cortical layers. Moreover, our LTPi-inducing protocol modifies firing of L5 PNs and alters the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All of these effects are captured by unbalancing the E/I ratio in a feedforward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength effectively influences the participation of single principal cortical neurons to cognition-relevant network activity.

https://doi.org/10.1016/j.celrep.2019.12.052

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VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours https://institutducerveau-icm.org/en/actualite/vegf-c-driven-lymphatic-drainage-enables-immunosurveillance-of-brain-tumours/ https://institutducerveau-icm.org/en/actualite/vegf-c-driven-lymphatic-drainage-enables-immunosurveillance-of-brain-tumours/#respond Fri, 17 Jan 2020 10:16:08 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18487 Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the For more information ]]> Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the characterization of the meningeal lymphatic network has shed light on previously unappreciated ways that an immune response can be elicited to antigens that are expressed in the brain1-3. Despite progress in our understanding of the development and structure of the meningeal lymphatic system, the contribution of this network in evoking a protective antigen-specific immune response in the brain remains unclear. Here, using a mouse model of glioblastoma, we show that the meningeal lymphatic vasculature can be manipulated to mount better immune responses against brain tumours. The immunity that is mediated by CD8 T cells to the glioblastoma antigen is very limited when the tumour is confined to the central nervous system, resulting in uncontrolled tumour growth. However, ectopic expression of vascular endothelial growth factor C (VEGF-C) promotes enhanced priming of CD8 T cells in the draining deep cervical lymph nodes, migration of CD8 T cells into the tumour, rapid clearance of the glioblastoma and a long-lasting antitumour memory response. Furthermore, transfection of an mRNA construct that expresses VEGF-C works synergistically with checkpoint blockade therapy to eradicate existing glioblastoma. These results reveal the capacity of VEGF-C to promote immune surveillance of tumours, and suggest a new therapeutic approach to treat brain tumours.

PubMed link

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The ICM, member of a major international program on the genetics of Parkinson’s disease https://institutducerveau-icm.org/en/actualite/the-icm-member-of-a-major-international-program-on-the-genetics-of-parkinsons-disease/ https://institutducerveau-icm.org/en/actualite/the-icm-member-of-a-major-international-program-on-the-genetics-of-parkinsons-disease/#respond Tue, 24 Dec 2019 09:22:36 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18328 The ASAP (Aligning Science Across Parkinson's (ASAP) Initiative) announced the launch of the Global Parkinson's Genetics Program (GP2), a major international For more information ]]> The ASAP (Aligning Science Across Parkinson’s (ASAP) Initiative) announced the launch of the Global Parkinson’s Genetics Program (GP2), a major international research program on Parkinson’s disease in which the Institut du Cerveau – ICM is involved.

 

Genetics plays an important role in Parkinson’s disease and several risk factors have already been identified. The progress in the genetics of this disease has a global impact on its understanding and the development of therapeutic solutions.

However, there is still much to be learned about the influence of genetics on the disease. Being a carrier of risk factors does not mean that the disease will develop, and even among those who develop the disease, differences in the age of onset or its evolution suggest the existence of other “protective” factors.

 

The Global Parkinson’s Genetics Program has three aspects:

– To deepen current knowledge about the genetic architecture of Parkinson’s disease.

– Accelerate the discovery and validation of new genetic mutations involved in diseases.

– Provide training and resources for scientists and clinicians.

 

“To understand more precisely the full extent of the influence of genetics in Parkinson’s disease, it is necessary to analyze data from a very large number of subjects, 150,000, sick or not. This is the goal of this major Global Parkinson’s Genetics Program (GP2). The study of very diverse populations from around the world will also allow us to fill a major gap in our knowledge of Parkinson’s disease. By bringing together expert centers around the world on Parkinson’s disease such as the Institut du Cerveau – ICM, we are joining forces to advance our understanding of the disease’s mechanisms and, ultimately, the development of treatment. ” Prof Alexis Brice, Institut du Cerveau – ICM Executive Director and member of the Steering Committee of the GP2 program.

 

For more information: https://parkinsonsroadmap.org/asap-announces-new-resource/

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Identifying neuronal correlates of dying and resuscitation in a model of reversible brain anoxia https://institutducerveau-icm.org/en/actualite/identifying-neuronal-correlates-brain-anoxia/ https://institutducerveau-icm.org/en/actualite/identifying-neuronal-correlates-brain-anoxia/#respond Mon, 23 Dec 2019 10:52:35 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18319 The team led by Prof. Stéphane CHARPIER (Sorbonne Université) at the Brain and Spine Institute is describing live for the first time the neuronal changes during For more information ]]> The team led by Prof. Stéphane CHARPIER (Sorbonne Université) at the Brain and Spine Institute is describing live for the first time the neuronal changes during reoxygenation of the brain in anoxia in an experimental in vivo model.

Abstract

We developed a new rodent model of reversible brain anoxia and performed continuous electrocorticographic (ECoG) and intracellular recordings of neocortical neurons to identify in real-time the cellular and network dynamics that successively emerge throughout the dying-to-recovery process. Along with a global decrease in ECoG amplitude, deprivation of oxygen supply resulted in an early surge of beta-gamma activities, accompanied by rhythmic membrane depolarizations and regular firing in pyramidal neurons. ECoG and intracellular signals were then dominated by low-frequency activities which progressively declined towards isoelectric levels. Cortical neurons during the isoelectric state underwent a massive membrane potential depolarizing shift, captured in the ECoG as a large amplitude triphasic wave known as the “wave-of-death” (WoD). This neuronal anoxic depolarization, associated with a block of action potentials and a loss of cell integrative properties, could however be reversed if brain re-oxygenation was rapidly restored (within 23.5 min). The subsequent slow repolarization of neocortical neurons resulted in a second identifiable ECoG wave we termed “wave-of-resuscitation” since it inaugurated the progressive regaining of pre-anoxic synaptic and firing activities. These results demonstrate that the WoD is not a biomarker of an irremediable death and unveil the cellular correlates of a novel ECoG wave that may be predictive of a successful recovery. The identification of real-time biomarkers of onset and termination of cell anoxic insult could benefit research on interventional strategies to optimize resuscitation procedures.

Source

*Adrien E. Schramm, Antoine Carton-Leclercq, Shana Diallo, Vincent Navarro, Mario Chavez, Séverine Mahon, and Stéphane Charpier. Identifying neuronal correlates of dying and resuscitation in a model of reversible brain anoxia. Progress in Neurobiology. DOI :10.1016/j.pneurobio.2019.101733

 

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New team leader at ICM! Jaime de Juan-Sanz https://institutducerveau-icm.org/en/actualite/jaime-de-juan-sanz-icm/ https://institutducerveau-icm.org/en/actualite/jaime-de-juan-sanz-icm/#respond Tue, 17 Dec 2019 10:30:47 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18271 Jaime de Juan-Sanz holds The Diane Barrière Chair « Molecular physiology of synaptic bioenergetics ». We met him in is new lab to talk about his background and For more information ]]> Jaime de Juan-Sanz holds The Diane Barrière Chair « Molecular physiology of synaptic bioenergetics ». We met him in is new lab to talk about his background and research projects.

What is your background before coming to Institut du Cerveau – ICM?

I did my PhD in Spain, at the Center for Molecular Biology Severo Ochoa in Madrid. I studied glycine transporters, in particular GlyT2. Mutations in this transporter cause a disease called hyperekplexia, a neurological disorder characterized by pronounced startle responses to tactile or acoustic stimuli and hypertonia. In my PhD I worked on understanding the molecular mechanisms controlling this protein to provide more insights to understand this disease. Then I moved to the United States at the Weill Cornell Medical College in New York City to study the molecular mechanisms that control synaptic function in the lab of Timothy Ryan. There, we developed new biosensors to study novel biology of axonal organelles such as the endoplasmic reticulum and mitochondria. This was very useful to see things we could not see before, which allowed us to learn many new aspects of how synapses work.

When did you know you wanted to do neuroscience?

When I was studying at the University actually… to me it really was the most interesting issue. Neuroscience is a very complex piece of biology. I thought it was very interesting back in the day, but I still think the same today. Understanding how the brain works is a crazy task we are all trying to do together and it really is an exciting challenge.

What led you to Institut du Cerveau – ICM?

One thing I really like about Institut du Cerveau – ICM is that it is very focused on neuroscience. I really love having all my colleagues doing many very different things at all scales, from clinical trials to molecular biology, to circuits, diseases… I think it is a very good place for me to learn more about the many things in neuroscience that I am not an expert on, but also it will give me the opportunity to help others with my knowledge in molecular neurobiology, imaging and biosensors.

What will your research at Institut du Cerveau – ICM be about?

My research holds two different aspects: one more basic and one more related to pathology. The first one is to understand how neuronal communication is sustained by neuronal metabolism. The brain consumes a lot of our daily energy intake. Synapses in particular, which connect neurons to one another, are actually highly energy-consuming. Every time neurons communicate with each other a lot of energy is consumed during the process. Not surprisingly, not having enough energy to sustain neuronal communication leads to deleterious effects. The first aim of my research is to understand what are the essential molecular actors involved in sustaining bioenergetics in healthy synapses. The second aim, more related to pathology, is based on the hypothesis that impaired bioenergetics may cause epilepsy. 170 different mutations in humans that affect the function of mitochondria, the organelle that provides energy in the cells, cause epilepsy. My idea is to work on developing a better understanding at the molecular level of how things are failing in synapses from an energetic point of view when mitochondria are dysfunctional and see whether this is influencing the development of epilepsy.

What collaboration would like to set up here at Institut du Cerveau – ICM?

I will collaborate with Vincent Navarro and Stephanie Baulac on epilepsy for sure. We are currently discussing what we can do together. I am working mainly with rats and mice models but if we can get human samples from epileptic brains at some point, we could try to translate some of our work in humans. Also, I would like to collaborate with Nelson Rebola, we have common interests in understanding synaptic function. My idea is to move some of our novel tools into brain slices with Nelson to explore the synaptic role of organelles in intact tissue.

will give me the opportunity to help others with my knowledge in molecular neurobiology, imaging and biosensors.

What will your research at Institut du Cerveau – ICM be about?

My research holds two different aspects: one more basic and one more related to pathology. The first one is to understand how neuronal communication is sustained by neuronal metabolism. The brain consumes a lot of our daily energy intake. Synapses in particular, which connect neurons to one another, are actually highly energy-consuming. Every time neurons communicate with each other a lot of energy is consumed during the process. Not surprisingly, not having enough energy to sustain neuronal communication leads to deleterious effects. The first aim of my research is to understand what are the essential molecular actors involved in sustaining bioenergetics in healthy synapses. The second aim, more related to pathology, is based on the hypothesis that impaired bioenergetics may cause epilepsy. 170 different mutations in humans that affect the function of mitochondria, the organelle that provides energy in the cells, cause epilepsy. My idea is to work on developing a better understanding at the molecular level of how things are failing in synapses from an energetic point of view when mitochondria are dysfunctional and see whether this is influencing the development of epilepsy.

What collaboration would like to set up here at Institut du Cerveau – ICM?

I will collaborate with Vincent Navarro and Stephanie Baulac on epilepsy for sure. We are currently discussing what we can do together. I am working mainly with rats and mice models but if we can get human samples from epileptic brains at some point, we could try to translate some of our work in humans. Also, I would like to collaborate with Nelson Rebola, we have common interests in understanding synaptic function. My idea is to move some of our novel tools into brain slices with Nelson to explore the synaptic role of organelles in intact tissue.

What is your hope in research?

My hope is to understand much better the rules controlling how neurons communicate with each other. This will help the scientific community to better understand how the brain works but also to understand how synaptic dysfunction may contribute to different diseases of the nervous system. A detailed understanding of a disease is essential to find a cure.

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