NeuroTime

Time in perception and action

The processing of time in the nervous system plays an adaptive role and altered interactions between different time scales lead to many pathologies. Indeed, the nervous system integrates, transmits and stores information from the millisecond to the year, while being under the constant influence of internal and external environmental factors. The NeuroTime axis studies the fundamental mechanisms of this temporal organisation in the nervous system and the pathological consequences of its disorganisation in order to develop innovative therapies:

  • study of the functional organisation of the nervous system from the millisecond to the year
  • study of the temporal disorganisation of the nervous system
  • therapeutic approaches for the temporal reorganisation of the nervous system

NeuroTime involves 13 NeuroStra teams associated with two platforms using state-of-the-art technologies to study biological rhythms in various animal (Chronobiotron) and human (CIRCSom) models.

Research teams

Intracellular membrane trafficking in the nervous and endocrine systems

Leaders: Dr. Stéphane GASMAN et Dr. Nicolas VITALE
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

We study the fundamental mechanisms of the temporal organisation and disorganisation of cell communication in the nervous and neuroendocrine systems. Indeed, this communication relies on the secretion of informative molecules, a process highly regulated in time by intense membrane trafficking (exocytosis, endocytosis, vesicular transport). We decipher the molecular mechanisms that control these different trafficking steps and reveal the alterations that underlie important pathologies (mental retardation, neuroendocrine cancers, obesity...). Using neurons, neuroendocrine cells or ependymal cells, we study more particularly the mechanisms that allow different lipids and proteins to control all the stages of the vesicle's life, from biogenesis to membrane fusion, including their transport within the cells.

Light, vision and the brain

Leaders: Dr. Marie-Paule FELDER-SCHMITTBUHL et Dr. Frank PFRIEGER
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team is studies the importance of light in the synchronisation of daily physiological functions, both in the brain and in the eye, and the role that the retina plays in these processes. In the context of today's society, which is subject to chronic jet lag ("social jet lag", shift work, etc.), we are studying more specifically the health impacts of repeated exposure to aberrant light cycles: effects on the retina, on food intake and metabolism, on addictive and aggressive behaviour.

Circadian clocks and metabolism

Leader: Dr. Étienne CHALLET
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team aims to identify the pathways by which brain clocks control the rhythmicity of physiological processes, including daily rhythms of food intake and meal anticipation, and how these rhythms are regulated by signals related to arousal and food ingestion in nocturnal and diurnal animal models.

Neuroendocrine rhythms of reproduction

Leader: Dr. Valérie SIMONNEAUX
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team studies the central and endocrine mechanisms that control the various rhythms related to reproductive activity in mammals. A very large number of biological systems, from cellular activity to physiological functions, present recurrent rhythms, notably daily and seasonal, which allow organisms to anticipate and adapt to changes in their environment. The team's research projects focus in particular on analysing the neuro-endocrine circuits involved in 1) the control of ovarian rhythms in female mammals (menstrual in humans, oestral in rodents) and particularly the occurrence of the pre-ovulatory LH peak at the interface of periods of rest and activity; 2) in the control of annual reproductive rhythms, whether they are regulated by the seasons via melatonin, by long-term endogenous phenomena such as the circannual clock, or during gestation by a maternal photoperiodic programming phenomenon. More recently, the team is analysing the effect of environmental disturbances (endocrine disruptors, light pollution, shift work) on reproductive cycles and fertility.

Circadian clock, sleep and homeostatic plasticity in mood disorders

Leader: Dr. Tsvetan SERCHOV
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team studies the molecular and cellular mechanisms of rapid antidepressant treatment. Using a combination of molecular biological methods, in vivo electrophysiology and complex behavioural analyses, we are investigating the role of the circadian clock and homeostatic sleep mechanisms as modulators of homeostatic plasticity in the pathophysiology and treatment of mood disorders.

Epigenetics and dynamics of memory systems

Leaders: Dr. Anne-Laurence BOUTILLIER et Pr. Jean-Christophe CASSEL
Research unit: Laboratory of Cognitive and Adaptative Neuroscience (LNCA) UMR 7364

The team's research focuses on the functional dynamics of memory consolidation and on the molecular and cellular mechanisms - particularly epigenetic mechanisms - responsible for memory deficits in neurodegenerative diseases (Alzheimer's disease and related disorders, Lewy body and frontotemporal dementias, Huntington's disease). We study the fundamental mechanisms that govern memory processes, with a particular interest in the hippocampal-cortical axis and the role of the reunited/romboid nuclei in the systemic consolidation of spatial memory, or the hippocampal-striatal-cortical axis in the systemic consolidation of procedural memory (engagement/disengagement of structures; cooperation vs. competition; behavioural flexibility) using dedicated behavioural tests, coupled with lesional approaches (excitotoxic, selective lesions) or AAV injection tracing. We are looking for epigenetic/transcriptomic signatures associated with memory formation (integrated analyses by high-throughput sequencing: RNA-seq, ChIP-seq...), in specific brain regions. The studies conducted in our team include characterisation from the molecular to the behavioural scale.

ENGRAM

Leaders: Dr. Chantal MATHIS et Dr. Lucas LECOURTIER
Research unit: Laboratory of Cognitive and Adaptative Neuroscience (LNCA) UMR 7364

ENGRAM aims to identify the neural networks involved in the elaboration and reactivation of a memory engram during spatial memory, recognition or fear conditioning tasks. The fate of these networks is also studied during ageing and in pathological conditions (mainly models of Alzheimer's disease and depression). Early biomarkers of Alzheimer's disease: we are evaluating the earliest markers of cognitive decline and alterations in neuronal networks in parallel with the emergence of neuropathological signs characteristic of Alzheimer's disease in mouse models. Spatial information coding: using multi-site recording and intracerebral calcium imaging in a mouse learning a spatial navigation task, we characterise the activity patterns at each stage of its trajectory to determine the dynamics of interactions between the different neural networks involved during learning. Housing conditions and cognitive ageing in rats: we evaluate the effects of an enrichment of housing conditions on the decline of certain cognitive functions and look for neurobiological correlates of successful ageing by focusing on the study of the cholinergic and endocannabinoid systems.

Central and peripheral mechanisms of neurodegeneration

Leader: Dr. Luc DUPUIS
Research unit: Inserm unit "Central and peripheral mechanisms of neurodegeneration" UMR_S 1118

Our laboratory aims at deciphering the pathological mechanisms that trigger Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia, two closely related fatal and currently untractable neurodegenerative diseases. Our originality lies in the study of the reciprocal interactions that occur between the central nervous system and the peripheral organs, and the general aim of understanding the myriad of signs and symptoms associated with these diseases.

Cognitive neuropsychology and physiopathology of schizophrenia

Leader: Dr. Anne GIERSCH
Research unit: Inserm unit "Cognitive neuropsychology and physiopathology of schizophrenia" UMR_S 1114

Research on the pathophysiology of psychiatric illnesses involves understanding what enables us to be connected to our environment, to be able to tell our story, to pay attention to our environment, to perceive it and to react to it in an adapted way. The alteration of these mechanisms raises questions about memory and time, which are explored in the unit, as well as psychological suffering and addiction-related symptoms.

Creativity, Science, Innovation

Leader: Pr. Thierry BURGER-HELMCHEN
Research unit: Bureau of Theoretical and Applied Economics (BETA) UMR 7522

The work of researchers in economics and management involved in the "Time in perception and action" theme aims to understand the behaviour of economic agents, taking into account their interactions (both on and off the market) and the risky and/or uncertain context in which they operate. Economists are particularly sensitive to the notion of behaviours, biases and noises that affect the decisions of individuals and their actions. This work is in line with the theories developed by Nobel Prize winners Richard Thaler, Daniel Kahneman and Vernon L. Smith. The Beta researchers use the methods of experimental economics in their work. The concept of time is used in the context of work on evolutionary economics and management, organisational change, individual routines and learning effects, ideation and the diffusion of innovations.

Integrative Multimodal Imaging in Healthcare

Leader: Dr. Laura HARSAN
Research unit: Integrative Multimodal Imaging in Healthcare team (IMIS) within The Engineering science, computer science and imaging laboratory (iCube) UMR 7357

Plasticity of pain controls

Leader: Pr. Pierrick POISBEAU
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our basic and clinical research team is interested in issues related to pain in the newborn and the adult (NeuroPain theme), but also considers these issues from the perspective of temporality (NeuroTime): 1) Functional exploration of pain: pain is a life history, the functional exploration carried out in our studies takes into account the maturation of the nervous system as a function of age and other differences such as biological sex or biopsychosocial influences (genetics, socio-cultural influences, quality of life including sleep and work life rhythms). 2) Ontogeny of nociception: the sensory coding of pain in its perception, visualised by the different cerebral oscillations, can identify the establishment of pain consciousness. However, the shaping of the motor response may be more difficult to assess. It therefore requires chronobiological characterisation in its early expression. 3) Neurodevelopmental consequences of early life stresses: we analyse the respective impact of painful and (a priori) non-painful stresses on the health trajectory of newborns. In particular, we study the role of oxytocin and vasoactive intestinal peptide. The monitoring of these biomarkers during the first 1000 days of life seems to provide valuable information on the plasticity of the nociceptive system in the context of a traumatic life history in infancy.

Sleep,  Clock, Light & NeuroPsychiatry

Leader: Pr. Patrice BOURGIN
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212



Platforms

Chronobiotron (UMS 3415)

Director: Dr. Sophie REIBEL FOISSET

The Chronobiotron is a platform for housing and functional exploration of rodents which has the particularity of having equipment specifically designed for the study of biological rhythms, all the mechanisms put in place by organisms to anticipate and therefore adapt to cyclical variations in their environment.

International research center on chronosomnology | CIRCSom

Director: Pr Patrice BOURGIN

The CIRCSom offers a clinical research platform for the study of the mechanisms of sleep regulation and vigilance in humans, from infancy to the elderly. The CIRCSom allows the study of patients with severe neuropsychiatric disorders, including children. The research team brings together all the skills, expertise and techniques necessary to carry out controlled research protocols, known as chronobiological, allowing the effects of light, sleep regulation mechanisms and EEG to be evaluated.

ComptOpt - Behaviour and Optogenetics

Directrice : Dr Mélanie KREMER

In coordination with the Chronobiotron UMS 3415, the "Behaviour and Optogenetics" or "ComptOpt" animal experimentation platform specialises in the study of behaviour in rodents (rats, mice and non-conventional species such as hamsters). ComptOpt designs, develops, adapts and implements new methodologies (models, tests and protocols) for animal biology research on the nervous system and its associated disorders. It also coordinates the transfer of know-how in animal experimentation on these research themes. We respond to the more specific needs in surgery and behaviour of teams working on the neurobiology of rhythms or sleep.

Read last issue