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Principles and mechanisms underlying the incorporation of newborn neurons into mature neuronal circuits – newbornNeurons
Neurogenesis is the process that forms functional neural tissue by the differentiation of neural stem cells into neurons, oligodendrocytes and glia. It takes place in specific ventricular niches and starts during embryogenesis, peaks in early development and it is still present in restricted brain r
Contribution of somatic and dendritic targeting cerebellar interneurons to temporal coding of sensory context – IntTempComp
The cerebellum is critical for fine-tuning behaviors under specific sensory contexts. How its microcircuitry generates temporally precise and context-dependent neural activity remains an open question. We hypothesize that the specific properties of soma- and dendrite-targeting interneurons (STIs and
Plasticity of intrinsic neuronal excitability in visual thalamic neurons – PLASTINEX
The dorsal lateral geniculate nucleus (dLGN), a primary recipient structure of retinal inputs, is traditionally considered to be just a relay of visual information. However recent works indicate that dLGN expresses functional plasticity following monocular deprivation (MD). Our proposal therefore co
Electrophysiologic, Morphologic and Trancriptomic plasticity in spinal dorsal horn Inhibitory networks to decipher atypical sensory perception. – EMTSens
Our body is constantly processing a wide range of sensory information that enables us to interact with our environment. Among these, somatosensory information is involved in many crucial functions, ranging from detection of potentially harmful stimuli to social interactions within a group. Somatosen
Untangling the selectivity of alpha-synuclein pathology transmission in synucleinopathies: role of intra- and extracellular environments – SYNSELECT
Synucleinopathies encompass several neurodegenerative diseases such as Parkinson’s disease, Dementia with Lewy bodies and multiple system atrophy (MSA). These diseases are characterized by the accumulation of proteic aggregates enriched in fibrillar alpha-synuclein (asyn) in the brain of patients. O
Maturation of locomotor networks in Danionella Translucida: from behavior to whole-brain imaging and circuit inference. – LocoMat
Most animals are born with a minimal set of behaviors that is progressively enriched during development to accommodate new internal needs, physical and environmental constraints. The emergence of these new functional capacities reflects the concurrent maturation of the brain circuitry, as new neuron
Development and Plasticity of the Auditory Cerebrovasculature – VAMPHEARS
By 2050, 900 million people will be affected by hearing disorders, mostly age-related hearing loss owing to the aging of the world population and the increasing exposure to noise. Hearing loss deeply modifies the neuronal activity of auditory networks, but less attention has been given to its effect
Long non-codingRNAs as regulators of microRNA function: A counting mechanism for neuron production? – UNCODING
Neurogenesis is a temporally and quantitatively highly orchestrated process. During early phases, neural stem cells divide symmetrically to amplify the radial glia progenitor pool precisely to the needed size. With onset of neurogenesis, these progenitors undergo a phase of clonal expansion that lea
Neuron-glia crosstalk during neuronal remodeling – ORIO
Models explaining overall glia-mediated axonal pruning converge on the hypothesis that glial cells are attracted to sites of pruning by a soluble recruitment signal that binds receptors at the glial cell surface. In Drosophila, such a “find-me/eat-me” signal has been thought to be secreted by the ne
APP fragment Aeta as key neuromodulator of synaptic NMDA receptors – APPYSYNAPSE
These last thirty years, studies on the amyloid precursor protein (APP) focused mainly on the synaptotoxicity of one of its fragments, the amyloid-ß (Aß) peptide, in the context of Alzheimer’s disease. Yet, APP, physiologically cleaved, allows the secretion of Aß but also of many other peptides incl
Exploring immune-related pathways in familial forms of Parkinson’s disease – IMMUNE-PARK
Chronic microglial activation is a well-described feature of Parkinson’s disease (PD), but whether microglia play an actual role in the disease onset and how they contribute to neuronal degeneration remains poorly understood. Recent discoveries in familial PD forms linked to the PRKN and LRRK2 genes
Neural basis of motor action gating by Arkypallidal globus pallidus neurons in function and dysfunction – MOTOR-GATE
Our daily actions whether habitual or goal-directed require adapted motor behaviors that are controlled by a set of brain regions called the basal ganglia (BG). The BG form a complex loop of nuclei connecting the cortex to the thalamus and they key role in motor action is probably best illustrated b
Impact of metabolic variations on corticospinal neuron production, circuit formation and pathology – MetaCSN
Precise voluntary movements are controlled by the corticospinal neuronal (CSN) circuit that wires together projection neurons positioned deep in the cortex and motor neurons located in the spinal cord with a final output on muscle contraction. This circuit is assembled during gestation and postnatal
Adult brain plasticity in the context of myelin repair: How neuronal cells generate oligodendrocytes – GOLIGO
The myelin sheaths produced by oligodendrocytes are essential elements in the central nervous system for the proper functioning of neurons by providing trophic and metabolic support to axons and by increasing the efficiency and speed of nerve impulse conduction. Demyelination, the pathological loss
Engram of fast learning in the striatum – EngFlea
Although the striatum is classically viewed as stakeholder of procedural learning, there is high evidence it also encodes for fast learning. Fast learning, a crucial component in daily life memory acquisition, involves one-shot learning experiences and elicits sparse neuronal activity. We (Partners
Dual N-glycosylation of AMPA receptors and impact on synaptic transmission and plasticity – DYNAGLYCS
More than 75% of membrane proteins are modified by addition of complex sugars through N-glycosylation. Congenital N-glycosylation defects, especially in the brain, result in usually lethal developmental disorders, while milder forms lead to mental retardation. Despite having a central role in the br
Functional and transcriptional profiling of satellite oligodendrocytes and host neurons in neocortical circuits – CORTEX-OL
In the neocortex functional interactions between neurons and glial cells contribute to many cellular and cognitive processes. Neurons in the cortex of many animals have associated glial cells, but we have little knowledge about the function of this cellular interaction. In this proposal we will focu
How does microglial activation impair the corneal pain network – CONNECTPAIN
Nociceptive pain is a physiologic response to a noxious stimulus whereas neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. In the ocular surface, and more specifically in the cornea, all of these physiological and pathophysiological conditions can occur. However,
Integration and gating in high-order sensory thalamus – Pom-Pom
The thalamus is a central brain structure that is essential for the proper functioning of the cerebral cortex, where the most elaborate brain computations take place. Within the thalamus, the “first-order” nuclei relay information from subcortical structures to the cortex, while “high-order” nuclei
Mollecular and cellular bases of the magnetic sense in a natural cryptochrome-knockout animal model – NOCRYMAGSENS
It is now well established that animals utilize the geomagnetic field in order to perform navigational tasks. However, the mechanisms by which specialized cells convert magnetic field changes into an electrical signal remain largely unknown. Three hypotheses are favoured in the field: A photochemica
Role of early thalamocortical axons in shaping the development of the primate cortex – ThaCoPrim
The project addresses the role of embryonic thalamocortical axons (TCA) on the early specification of cytoarchitecturally distinct areas in the primate cortex, via the control of progenitors cell-cycle and fate. Building on unpublished findings from Dehay and Molnar, the thalamo-cortical interaction
Hypothalamic regulation of REM sleep – HYPREM
Background The hypothalamus regulates homeostatic processes across many physiological functions, including energy metabolism, feeding behavior, thermoregulation and sleep. Our groups in Bern and Lyon have played seminal roles in elucidating the role of the lateral hypothalamus (LH) in controlling R
Contextual fear memory: consolidation by the combined action of serotonin and microglia. – FEARMISER
Contextual fear memory is a conserved, still mysterious, process allowing vital response to dangerous situations. Microglia, which are the resident macrophages of the brain, are known to contribute to synaptic remodeling, by eliminating or promoting the appearance of synapses, and it has recently be
Role of dorsal Prosubiculum monoamine signaling in salience detection – SubDOPA
Detection of salient stimuli or environmental changes is a key mechanism that facilitates associative learning by allocating attentional resources toward biologically significant. The detection of salience is highly dynamic and influenced by a wide range of factors, including past experiences, arous
Dissecting the impact of bacteria-derived peptidoglycan on neuronally controlled behaviors – pepneuron
An increasing body of evidence indicates that microbes, which live closely associated with animals, significantly influence their behavior. The extreme complexity of the nervous system of animals combined with the extraordinary microbial diversity are two major obstacles to understand, at the molecu
The role of tubulin detyrosination in the acquisition of neuronal polarity. – NeuroSym
Neurons are highly polarized cells, which assemble a single axon and several dendrites. However, it still remains unclear how neuronal polarity is established. Accumulating evidence suggest that microtubule (MT)-based cytoskeleton plays an essential role in the establishment and maintenance of neuro
Roles of mTOR pathway in glial development and in TORopathies – TOROGLIE
Multiciliated ependymal cells line all brain ventricles and play major role for the flow of cerebrospinal fluid (CSF). Together with their sister cells, adult neural stem cells (NSC), they compose the adult neurogenic niche from which new neurons are continuously produced. Ependymal cells are produc
Conserved functions of dopaminergic circuits for aversive value-based learning – DOPAVALUE
While extensive research described how valuation circuits signal absolute aversive value (more or less bad) to experience during learning, much less is known on how such circuits operate to compute relative aversive value (better or worse than). Recent models propose that the dopaminergic circuits a
An endocannabinoid-induced switch in cortical disinhibitory circuits – CADICI
Sensory information processing originates from the concerted action between pyramidal neurons and a plethora of interneuron (INs) types. In superficial layers of the mouse primary visual cortex (V1), vasoactive intestinal peptide (VIP) INs are considered specialists of disinhibition. Notably, our pr
Decoding contextual information processing by cortical layer 1 microcircuits – DecoSensoL1
Sensation during wakefulness can occur under drastically different conditions leading to variability in perceptual outcomes. This flexibility in the computation of incoming signals appears to be a key feature of cortical processing in the healthy brain. However,the mechanisms of such adaptability in
Opto-pharmacological dissection of nicotinic signaling in the medial habenulo-interpeduncular axis – CHOLHAB
Smoking remains the major cause of preventable death in humans. Worldwide, 100 million people are expected to die this century from the consequences of prolonged tobacco consumption and of the ensuing addiction to nicotine. In the brain, nicotine acts through nicotinic acetylcholine receptors (n
Cell-type specific determinants of epileptogenic cortical malformations – EPIDEV
EPIDEV is a 514k€ basic research collaborative project involving 2 French partners and a Swiss partner over 42 months. EPIDEV builds on the recently recognized concept that the human brain is a genetic mosaic arising from somatic postzygotic mutations during development. Brain mosaicism is impli
HTT controls CNS regeneration via specific mRNA translation – RHIRE
In our modern societies, the rate of nervous system disorders is continuously growing and represents a major public health issue. Indeed, our lifestyle and the substantial ageing of the population participate to the massive development of neurodegenerative diseases and traumatic injuries. As of toda
Regulation of neuronal chloride transport by gangliosides: a novel therapeutic prospect in epilepsy – GABGANG
The polarity of GABA signaling in the brain relies on transmembrane chloride gradients which are themselves regulated by cation/chloride cotransporters (CCCs). Intraneuronal chloride buildup promotes pathological activities in the human epileptic cortex and animal models of epilepsy. It is therefore
Internalization of hippocampal functions during development – DevHippo
The ability to acquire knowledge and build internal models of our surrounding environment is critical for adaptive behavior. This internalisation process is at the core of various cognitive abilities, particularly those requiring us to represent information in the absence of direct sensory inputs or
Radial glial cells fibers as sensors of cortical development progression. – RGLISSDEV
Understanding how the cerebral cortex develops is the sine qua none condition for deciphering neurodevelopmental diseases and the associated pathophysiological mechanisms. Cortical neurons are generated by radial glial cells (RGCs) and the regulation of their fate behavior and lineage progression ar
Genetic factors of Alzheimer's disease and impact on the pathophysiological synaptic function – GENSYNALZ
Since Alzheimer’s Disease (AD) has a strong genetic component, knowledge of this genetic component would help identify relevant signalling pathways. We have been able to characterize genetic factors and the combination of this information with biological data has revealed that the synaptic loss obse
Functional plasticity of medullary descending motor tracts following spinal cord injury and regenerative stimulation – MedullaryWalk
This project aims to shed light on the neuronal mechanisms allowing motor recovery after spinal cord injury (SCI). More specifically, it will investigate the plasticity and functional relevance for locomotor recovery of specific descending neuronal tracts originating from the medulla. SCI is an
CRF-locus coeruleus interplay in mediating resilience against chronic stress – NoReSt
Major depression is a severe and far too common mental disorder. Its global burden poses a substantial challenge for our societies. Despite well-defined and evidence-based strategies that can address depression, less than half of patients suffering from this condition achieve remission with current
Uncovering subthalamic ex vivo alterations targeted by deep brain stimulation in cocaine addiction – SubStimCoc
In the quest for a treatment against addiction, pharmacological approaches have so far failed to produce consistent beneficial outcomes, especially concerning cocaine. Among the therapeutic strategies considered to tackle this societal burden, deep brain stimulation (DBS) is promising. A large amoun
PARK-PEP: Targeting LRRK2 phosphorylation with interfering peptides in experimental models of Parkinson’s disease – PARK-PEP
Parkinson's disease (PD) is one of the major degenerative diseases for which there is no cure. There is therefore a pressing need to identify mechanisms implicated in PD pathogenesis that can be targeted for therapy. In this context, LRRK2, one of the major genetic determinants of sporadic and famil
ß spectrin implication in dendritic spine shape and physiology – MorphoSpectrin
The dendritic spine, where the postsynaptic compartment of most excitatory synapses is localized, is a small protrusive structure emerging from the dendritic shaft. The molecular composition, the morphology and the compartmentalization of spines are critical for synaptic function. Moreover, spines a