M1 - Neuroscience

Behaviors—whether determined by conscious or unconscious processes—are based on complex neurobiological substrates. They are, in fact, 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 its species.

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

-Gene–Behavior

The Relationship Between Genotype and Phenotype—Environmental Impact—Attention 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 Bases of Emotions - Functions of Emotions - Maladaptation: Pathological Aspects: Emotional Disorders

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The Neuropsychopharmacology course covers the molecular, cellular, and integrated mechanisms underlying the mode of action of psychotropic drugs, using several disorders (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.). Drawing on advances in neurobiological research and their therapeutic applications in medication, the course aims to provide an understanding of 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 types of decisions that progressively determine the neural fate of cells and ensure their nervous function. The various stages considered are:

(i) the development of the nervous system

(ii) the specification of neurons

(iii) nervous 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.

-Roles of neurotrophic factors

-Functions of electrical activity

-Critical periods

-Roles of neuron-glial cell interactions.

-Neural stem cells

3) Developmental Disorders

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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 various themes:

1. Cytoskeleton: Introduction to the different types of cytoskeletons. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton that regulate 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 trafficking and targeting: Ubiquitination and the proteasome. Targeting to subcellular compartments; endocytosis and secretion pathways. The molecular basis of vesicular transport: budding, fusion, and molecular motors. Signaling in membrane trafficking; genetic diseases associated with trafficking; and hijacking by pathogens.

4. Cell Cycle: Historical Overview. Molecular Regulation of the Cell Cycle. The mitotic spindle, microtubule dynamics and molecular motors, mechanisms of chromosome attachment, checkpoints, regulation of mitotic exit, and cytokinesis. Mitotic abnormalities 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. Pathophysiological consequences of dysregulation of programmed cell death.

Various research models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

The program offers a review of key concepts 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 involved in 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 regulation during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

3. Addressing and cell traffic: Ubiquitination and the proteasome. Transport to subcellular compartments, endocytosis, and secretion pathways. The molecular basis of vesicular transport, budding, fusion, and molecular motors. Signaling in membrane trafficking, genetic diseases linked to trafficking, and disruption 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 mitotic 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 mechanisms of apoptosis; signaling pathways involved. Role in maintaining homeostasis. Pathophysiological consequences of dysregulation of programmed cell death.

Various study models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

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The EU will first address the main communication pathways between normal cells and intracellular signal transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, specifically their structure, function, and modulation by interacting proteins involved, in particular, in the phenomenon of desensitization. The main intracellular pathways activated by membrane-bound GPCRs will be discussed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca²⁺ homeostasis, as Ca²⁺ is a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular in the context of the lymphocyte response following antigenic 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 protective mechanisms against oxidative stress will also be examined.The following chapter will address the endocannabinoid system, which serves to summarize all the topics previously covered in the course. The endocannabinoid system is responsible for numerous central and peripheral regulatory processes.

Finally, two other topics will be covered: the blood-brain barrier, which provides a framework for discussing cellular communication in a highly integrated manner between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood glucose levels through insulin secretion.

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

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An internship lasting more than 4 months at an organization (research laboratory, company, etc.) in France or abroad

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The course is taught by faculty members from the departments of medicine, science, and pharmacy. It consists of 42 hours of lectures and supervised work divided into 7 themes (see Syllabus), including two series of article presentations: the first series focuses on articles selected by the instructors for each theme, and the second series features articles chosen by the students. At the end of each course unit, students organize a mini-symposium where the articles are presented. They write abstracts of these articles for the journal *Medecine-Sciences*.

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The physiology lab course allows students to record cardiac action potentials in a frog’s heart 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 EU TER course aims to prepare students to organize and conduct an in-depth literature review that will enable them to approach their internship with an understanding of the state of the art in the field, in particular to produce a relevant and well-thought-out introduction to their experimental work.

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