M1 - Neuroscience

Behaviors, whether determined by conscious or unconscious processes, are based on complex neurobiological substrates. They are underpinned by molecular and cellular changes within the nervous system that modulate the neural networks responsible for motor and emotional processes linked to an individual's memory. These processes are fundamental in enabling the organism to develop an integrated behavioral response in close interaction with its environment, thereby ensuring the adaptation and survival of the individual and their species.

The topics covered in the Behavioral Neurobiology course will be 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 genetic and epigenetic factors—The relationship between plasticity and memory—The neurobiology of memory, forgetting, and reconsolidation

-Neurobiology of emotions

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

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The neuropsychopharmacology EU deals with the molecular, cellular, and integrated mechanisms underlying the mode of action of psychotropic drugs, using a few pathologies (depression, schizophrenia, anxiety, etc.) as examples. It aims to understand how the principles of pharmacology apply specifically to mental disorders (e.g., pharmacodynamics, tolerance, physical and psychological dependence, etc.). Based on 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 gradually determine the neural fate of cells and ensure their nervous function. The different stages considered are:

(i) the genesis of the nervous system

(ii) the specification of neurons

(iii)nerve function: axonal guidance and connectivity

(iv) neural remodeling

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

-Synaptogenesis and the major stages of development.

-Roles of neurotrophic factors

-Roles of electrical activity

-Critical periods

-Roles of neuron-glial cell interactions.

-Neural stem cells

3) Developmental disorders

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The program offers refresher courses 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. Cellular addressing and trafficking: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. The molecular basis of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, genetic diseases related to trafficking, and hijacking by pathogens.

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

5. Stem cells: cell differentiation, totipotency, pluripotency, and multipotency; embryonic, adult, and cancer stem cells.

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

Various study models are presented to introduce the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in understanding 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, totipotency, pluripotency, 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 EU will first address the main communication pathways between normal cells and intracellular transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, namely their structure, function, and modulation by interaction proteins involved in particular in the phenomenon of desensitization. The main intracellular pathways activated by membrane GCRs will be addressed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigen stimulation. Furthermore, the production of oxygen free radicals, which cause 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 will allow us to recap all the topics previously discussed in the course. The endocannabinoid system is responsible for multiple central and peripheral regulations.

Finally, two other topics will be addressed: the blood-brain barrier, which allows for highly integrated cellular communication between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood sugar levels through insulin secretion.

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Two- to four-month internship in an organization (research laboratory, company, etc.) in France or abroad

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Internship lasting more than four months in an organization (research laboratory, company, etc.) in France or abroad

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Teaching is carried out by lecturers and researchers from the medical, science, and pharmacy departments. It consists of 42 hours of lectures and supervised work divided into seven themes (see Syllabus), including two series of article presentations: the first series on articles proposed by the lecturers for each theme covered, and the second series on articles chosen by the students. Students organize a mini-symposium at the end of the course where the articles are presented. They write summaries of these articles for the journal Medecine-Sciences.

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The physiology lab allows students to record cardiac action potentials in frog hearts using the intracellular microelectrode technique. This is a qualitative and quantitative method for measuring the electrical activity of the heart muscle.

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The TER aims to prepare students to organize and carry out an in-depth bibliographic analysis that will enable them to approach their internship with knowledge of the state of the art in the field, in particular in order to produce a relevant and thoughtful introduction to their experimental work.

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