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Scientific challenges

Given the frequency and cost of these diseases, it is evident that investment in research on neurological and psychiatric disorders is insufficient, especially in Europe, and therefore needs stepping up. It would nevertheless be wrong to justify or base funding for neuroscience research on this observation alone. Understanding the nervous system is a major challenge and remains a "barrier" to knowledge.

The human brain contains a hundred billion neurons, each one connected to thousands of others. These neurons are assisted by glial cells, which are ten times more numerous. The brain’s extraordinary ability to process information probably stems from the way it is organized (molecular and cellular). The major challenge of neurosciences is to analyze and assimilate the inherent complexity at all levels of the nervous system to understand the neural bases of higher cognitive functions and behaviors.

The neural code, behaviors and thought

Imaging in real time of the development of living neurons in cell culture, Institut de Neurobiologie de la Méditerranée (INMED), Marseilles

Imaging in real time of the development of living neurons in cell culture, Institut de Neurobiologie de la Méditerranée (INMED), Marseilles

Just as the “genetic code” has been deciphered (double helix structure of DNA, 1953 and sequencing of the human genome, 2001), research scientists today are endeavoring to model the "neural code", i.e. the way in which the interaction of nerve cells between themselves and with the environment produces higher functions than perception and cognition. This neural code therefore results from the functional interaction of neurons organized into multiple dynamic networks. Cracking the neural code is crucial for developing new human/machine interfaces and restoring cognitive defects in patients. The main scientific challenges are:

  • deciphering how the nervous system is organized at cell level (cellular and molecular biology, biophysics), modeling neuronal networks including glial cells, grasping the role of neurotransmitters and electrochemical communication in general;
  • defining the integration rules underlying the main sensory, motor, cognitive and behavioral functions by developing systemic approaches including, for example, behavioral genetics, ethology, evo-devo (evolutionary development biology);
  • identifying interaction rules of the human mind with its environment. How does the brain construct inferences, perceive time and space, form mental representations, verbal or non-verbal ideas, construct its experience via motivations and emotions and make decisions? These questions call for comparative analyses between the human and animal brain. The challenge here is to combine cognitive neurosciences and psychological, linguistic, philosophical and economic approaches.

Development, plasticity and aging of the nervous system

Imaging in real time of the development of living neurons in cell culture, Institut de Neurobiologie de la Méditerranée (INMED), Marseilles - P. Latron

Imaging in real time of the development of living neurons in cell culture, Institut de Neurobiologie de la Méditerranée (INMED), Marseilles

Genes interact with the environment at every stage when the functional nervous system is forming and contributes to its plasticity over time. Plasticity is an essential property of the nervous system, involved predominantly during growth and learning, which is so important for humans. Plasticity makes it possible to adapt to the environment throughout one’s lifetime and during pathological situations. In this sense, this approach is closely tied in with cracking the "neural code", explained above.

Some of the fundamental challenges are:

  • Identifying the respective role of genetic and epigenetic (expression-transcription of genes, chromatin remodeling) factors in the development of the nervous system: formation of neural ensembles, regionalization of the nervous system, neuron migration, differentiation between neurons and glial cells, establishment of connections and synaptogenesis. The influence of the environment on this development must be taken on board, as well as the way in which interaction between genetic polymorphisms and living conditions influences behavior.
  • Analyzing the characteristics of neuron stem cells, during embryogenesis and in adults. The point here is to understand their recruitment, differentiation and integration into neuron networks, and to determine whether these processes influence behavioral plasticity in adults, affect behavioral disorders (depression, stress) or bring about post-traumatic regeneration. Particular attention will be paid to the therapeutic potential and procedure of stem cells, in view of the hopes pinned on biotherapy.
  • Understanding neuronal ensembles, synaptogenesis (including synapse functioning and neurotransmission) and neuronal dynamics and plasticity during growth (critical periods), in adulthood, during aging and neuropsychiatric disorders. This aspect includes analyzing intra- and extracellular signaling networks controlling the architecture and dynamics of neurons and synapses.

Although their objectives and approaches differ, fundamental and clinical neurosciences raise the same questions and complement each other. In this context, it seems important to bridge the gap that may exist between fundamental discovery and therapeutic application by developing translational research. This means speeding up the time it takes for scientific discoveries to be applied in practice and vice-versa.

Indeed, unprecedented breakthroughs have been made regarding the physiopathology of hereditary disorders of the nervous system, sensory disabilities, neurological and psychiatric disorders and behavioral disorders. Shedding light on the molecular bases of numerous disorders of the nervous system gives an insight into the mechanisms of diseases, enabling a more specific nosology based on the pathogenic processes to be created and animal models to be developed that are increasingly similar to human pathology. This progress must now lead to an increase in patient care: diagnosis, prevention, treatment and rehabilitation. The spectrum of therapeutic agent delivery means is expanding (e.g. nanotechnologies) and the very nature of these agents is becoming more diverse. Alongside conventional pharmacology, there is considerable interest in stem cells. Biological therapeutic agents (growth or survival factors) are being actively sought and, resulting from fundamental research, small interfering RNAs are finding their place in the arsenal of gene therapy.

This expansion of fundamental research towards clinical research is also occurring in the opposite sense: clinicians are making observations that prompt biologists to raise new questions. This type of research implies the bringing together of an ensemble of multidisciplinary (physics, chemistry, biology, clinical research) and multi-institutional skills (academics, clinics and manufacturers).

Applying fundamental discoveries through human treatments particularly requires:

  • strengthening physiopathological research so as to improve understanding of the malfunctions behind the symptoms observed in neurological and psychiatric diseases and their innermost mechanisms;
  • facilitating the development of predictive and pertinent cell and animal models;
  • developing innovative therapeutic approaches and effective strategies for targeting drugs towards and in the nervous system so as to reduce the side effects of the therapeutic strategies developed, which too often lead to clinical failures;
  • identifying and validating new and if possible quantitative pertinent markers of neurological and/or psychiatric diseases;
  • organizing clinical research on neurological and psychiatric diseases into thematic networks and expert centers, to enable a high-quality phenotypical evaluation of large uniform groups of patients as well as the long-term follow-up of patient cohorts.
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