M1 - Neuroscience

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

The topics covered in the Neurobiology of Behavior EU will include:

-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 study synaptic plasticity: electrophysiology, optogenetics, animal models, behavioral tests-Regulatory factors of synaptic plasticity including genetics and epigenetics-Plasticity/memory relationship-Neurobiology of memory, forgetting and reconsolidation

-Neurobiology of emotions

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

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The neuropsychopharmacology course deals with the molecular, cellular and integrated mechanisms underlying the mode of action of psychotropic drugs, using a few pathologies as examples (depression, schizophrenia, anxiety, ....). It aims to understand how the principles of pharmacology are specifically declined in the context of psychological disorders (e.g. pharmacodynamics, tolerance, physical and psychic dependence,...). Based on the advances in neurobiology research and their therapeutic applications in medication, 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 progressively specify the neural fate of cells and ensure their nervous function. The different steps considered are:

(i) the genesis of the nervous system

(ii) the specification of neurons

(iii) nerve function: axonal guidance and connectivity

(iv) neuronal remodeling

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

-Synaptogenesis and major developmental milestones.

-Roles of neurotrophic factors

-Roles of electrical activity

-Critical periods

-Roles of neuron-glial cell interactions.

-Neuronal 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:

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.

Cellular Adhesion & Signaling: Adhesive structures cell-cell and cell-extracellular matrix, their molecular organization and dynamics. Functions and regulations 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, genetic diseases related to trafficking and detour by pathogens.

4.cell cycle:Historical introduction. Molecular regulation of the cell cycle. 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 the maintenance of homeostasis. Pathophysiological 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.

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 intracellular transduction pathways, encountered in physiological and neurophysiological mechanisms, will be discussed, such as G protein coupled receptors (GPCRs), their structure, function and modulation by interacting proteins involved in the desensitization phenomenon. The main intracellular pathways activated by GPCRs will be discussed (MAPkinase, PI3kinase, etc...).

Secondly, an important part of the course will focus on calcium signaling and Ca2+ homeostasis; Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigenic stimulation. Moreover, 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. In this context, the pathways of protection against oxidative stress will also be studied.The following chapter will address the endocannabinoid system which allows to recapitulate all the themes that will be evoked previously 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 allows to evoke the cellular communication in a very integrated way between two environments and the -pancreatic cell whose activity is crucial for the regulation of glycemia by the secretion of insulin.

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The aim of this course is to introduce functional genomics technologies and to present examples of biological questions that can be asked using them.

This unit aims to present "omics" functional genomics technologies, and some biological questions that they can address.The lectures are given by both associate professors and researchers.

Introduction to functional genomics: approaches, concepts and methods

An introduction to functional Genomics: approaches, concepts and methods

V. Coulon, UM / IGMM

Genome organization / Organisation des génomes

Techniques de séquençage / DNA sequencing methodsL. Journot, IGF

3D genome organization J. Poli, UM / IGH

Genome topological organisation and replication-V. Coulon, UM / IGMM

Régulation spatio-temporelle de l'expression des génomes / Spatio-temporal regulation of gene expressionTranscriptionEpissage / Splicing-V. Coulon, UM / IGMM

Non-coding RNAsV. Coulon, UM / IGMM

Interactomics / InteractomiqueIan Robbins, UM / IGMM

Proteomics and Pharmacogenomics / Protéomique et pharmacogénomiqueC. Bécamel, UM / IGF

Animal Models / Modèles animaux

Using Mice in Functional Genomics F. Poulat, IGH

La Drosophile en génomique fonctionnelle / Using Drosophila in Functional Genomics -F. Juge and S. Chambeyron, IGH

Scientificarticles analysis and presentation(15min + 10 min discussion per group of 3 students)

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Two to four month internship in a structure (research laboratory, company, etc.) in France or abroad

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

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The teaching is carried out by teacher-researchers from the UFRs of medicine, science and pharmacy. It is organized into 42 hours of classes and supervised work divided into 7 themes (see Syllabus) including 2 series of article presentations; the first series on articles proposed by the speakers of each theme. A second series on articles chosen by the students. The students organize a mini-colloquium at the end of the course where the articles are presented. They write short reports of these articles for the Medecine-Sciences magazine.

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The physiology laboratory course allows to carry out recordings of cardiac action potential on the frog heart by the intracellular microelectrode technique. This is a qualitative and quantitative method of measuring the electrical activity of the heart muscle.

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The aim of the TER course is to prepare the student to organize and carry out an in-depth bibliographical analysis in order to approach the internship with a knowledge of the state of the art in the field and to produce a relevant and well thought-out introduction to his experimental work.

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