M1 - Neuroscience

Behaviors, whether determined by conscious or unconscious processes, are based on complex neurobiological underpinnings: they are underpinned by molecular and cellular modifications within the nervous system, modulating neural networks at the origin of motor and emotional processes that are linked to the individual's memory. These processes are fundamental in enabling the organism to develop an integrated behavioral response in close interaction with its environment, ensuring adaptation and survival for the individual and its species.

The topics covered in the Neurobiology of Behavior course are as follows:

-Gene-behavior

The relationship between genotype and phenotype -Impact of the environment -Attentional processes/Movement planning -Behavioral disorders (genetic and environmental aspects)

-Memory and synaptic plasticity

Methodological approaches to studying synaptic plasticity: electrophysiology, optogenetics, animal models, behavioral tests-Factors regulating synaptic plasticity, including genetics and epigenetics-Plasticity/memory relationship-Neurobiology of memory, forgetting and reconsolidation

-Neurobiology of emotions

Neurobiological substrates of emotions -Emotional functions -Disadaptation: Pathological aspects: Emotional disorders

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The Neuropsychopharmacology UE covers the molecular, cellular and integrated mechanisms underlying the mode of action of psychotropic drugs, using a number of pathologies as examples (depression, schizophrenia, anxiety, ....). The aim is to understand how the principles of pharmacology are specifically applied to mental disorders (e.g. pharmacodynamics, tolerance, physical and psychological dependence, etc.). Based on advances in neurobiological research and their application to drug therapy, the course aims to understand the concepts underlying the treatment of psychiatric disorders.

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1) What is the genetic program underlying the development of the nervous system? This course highlights the type of decisions that gradually determine the neural destiny of cells and ensure their nervous function. The different stages considered are:

(i)the genesis of the nervous system

(ii)neuron specification

(iii)nerve function: axonal guidance and connectivity

(iv)neuronal remodeling

2) What molecular, cellular and environmental interactions control the development of the nervous system?

-Synaptogenesis and the major stages of development.

-The role of neurotrophic factors

-The role of electrical activity

-Critical periods

-The role of neuron-glial cell interactions.

-Neural stem cells

3) Developmental pathologies

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Teaching is done by teachers and/or researchers at the Faculties of Medicine, Sciences or Pharmacy, or at local research institutes.Course contents will be adapted to current scientific advances.

Teaching is organized in topics (lectures/tutorials, 4 to 5:30 hrs each);each includes an introduction and a seminar. In addition, for each topic, a group of students is in charge of presenting one or two recent scientific research articles.

Examples of subjects treated:

Immune adaptive responses, vaccination

Immune tolerance

Aging of the immune system

Metabolic regulation of the immune response

Immune response regulation by microbiota

Immune system-central nervous system interactions

Immunotherapy, therapeutic antibodies

The Unit is complemented by practical work by groups on a mini-research project that includes design of experiments, realization and analysis. Training is available in the use of flow cytometry data analysis software.Results are presented orally to the entire class.

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The program offers a refresher course and an in-depth study of the major concepts and methodologies of cell biology, organized around different themes:

1 Cytoskeleton:Introduction to the different types of cytoskeleton. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton and regulating polymerization. Molecular motors. Principles of cell migration.

2.cell adhesion & signaling: cell-cell and cell-extracellular matrix adhesive structures, their molecular organization and dynamics. Functions and regulation during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

3 Addressing and cell trafficking: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. Molecular basis of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, trafficking-related genetic diseases and pathogen detour.

4 Cell cycle: Historical introduction. Molecular regulation of the cell cycle. The mitotic spindle, microtubule dynamics and molecular motors, chromosome attachment mechanisms, checkpoints, regulation of mitosis exit and cytokinesis. Mitotic disorders associated with cancer cells.

5 Stem cells: cell differentiation, toti-, pluri- and multipotency, embryonic, adult and cancer stem cells.

6 Programmed cell death: Apoptosis, autophagy, necrosis. Stages and modalities of apoptosis, signaling pathways involved. Role in maintaining homeostasis. Pathophysiological consequences of deregulation of programmed cell death.

Different study models are presented, to introduce the importance of the contribution of biological diversity to the discovery of cellular and molecular mechanisms, and to the understanding of human pathologies.

The program offers a refresher of knowledge and an in-depth study of the major concepts and methodologies of cell biology, organized around different themes:

1. Cytoskeleton: Introduction to the different types of cytoskeleton. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton and regulating polymerization. Molecular motors. Principles of cell migration.

2. Cellular Adhesion & Signaling: Cell-cell and extracellular cell-matrix adhesive structures, their molecular and dynamic organization. Functions and regulations during development and pathogenesis. Regulation by signaling channels. Mechanotransduction.

3. Addressing and cell traffic: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. The molecular bases of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, genetic diseases linked to trafficking and diversion by pathogens.

4. Cell cycle: Historical introduction. Molecular regulation of the cell cycle. The mitotic spindle, microtubule and molecular motor dynamics, chromosome attachment mechanisms, checkpoints, regulation of mitosis output and cytokinesis. Mitotic disorders associated with cancer cells.

5. Stem cells: cell differentiation, toti-, pluri-and multipotency, embryonic, adult and cancer stem cells.

6. Programmed cell death: Apoptosis, autophagy, necrosis. Stages and modalities of apoptosis, signaling pathways involved. Role in maintaining homeostasis. Physiopathological consequences of deregulation of programmed cell death.

Different study models are presented, in order to introduce the importance of the contribution of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human pathologies.

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The main communication pathways between normal cells and the intracellular transduction pathways encountered in physiological and neurophysiological mechanisms will be covered, with a focus on G protein-coupled receptors (GPCRs) and their structure, function and modulation by interacting proteins, notably involved in desensitization. The main intracellular pathways activated by GPCRs will be discussed (MAPkinase, PI3kinase, etc.).

A major part of the course will then focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the lymphocyte response to antigenic stimulation. In addition, the production of oxygenated free radicals, at the origin of oxidative stress, is dependent on intracellular Ca2+. The physiological role of free radicals will be discussed, as well as their involvement in oxidative stress. The following chapter will focus on the endocannabinoid system, summarizing all the topics covered earlier in the course. The endocannabinoid system is at the origin of multiple central and peripheral regulations.

Finally, two other themes will be addressed: the blood-brain barrier, which evokes highly integrated cellular communication between two environments, and the -pancreatic cell, whose activity is crucial to the regulation of glycemia through insulin secretion.

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Two to 4-month internship in a research laboratory or company in France or abroad.

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Internship of more than 4 months in a facility (research laboratory, company, etc.) in France or abroad.

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Teaching is carried out by teacher-researchers from the UFRs of Medicine, Science and Pharmacy. It is organized into 42 hours of lectures and supervised work divided into 7 themes (see Syllabus) including 2 series of article presentations; 1 series on articles proposed by the lecturers in each theme. A second series on articles chosen by the students. At the end of the course, students organize a mini-colloquium at which the articles are presented. They write brief reviews of these articles for the journal Medecine-Sciences.

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The physiology practical course enables you to record cardiac action potentials on frog hearts using the intracellular microelectrode technique. This is a qualitative and quantitative method for measuring the electrical activity of cardiac muscle.

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The aim of the TER course is to prepare students to organize and carry out an in-depth bibliographical analysis, enabling them to approach their internship with a knowledge of the state of the art in the field, and in particular to produce a relevant and thoughtful introduction to their experimental work.

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