- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Neuroendocrine regulation and behavior
- bioluminescence and chemiluminescence research
- Retinal Development and Disorders
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Ion channel regulation and function
- Insect and Pesticide Research
- Molecular Sensors and Ion Detection
- Cholinesterase and Neurodegenerative Diseases
- Neurobiology and Insect Physiology Research
- Primate Behavior and Ecology
- Adenosine and Purinergic Signaling
- Computational Drug Discovery Methods
- Click Chemistry and Applications
- Mental Health Research Topics
- Chemical Synthesis and Analysis
- Luminescence and Fluorescent Materials
- Olfactory and Sensory Function Studies
- Animal Behavior and Reproduction
Centre National de la Recherche Scientifique
2016-2025
Laboratoire Plasticité du Cerveau
2021-2025
ESPCI Paris
2021-2025
Université Paris Sciences et Lettres
2021-2025
Sorbonne Université
2012-2024
Neurosciences Paris-Seine
2016-2024
Inserm
2017-2024
Institut de Biologie Paris-Seine
2017-2024
Université Paris-Seine
2016-2023
Institut de Neurophysiopathologie
2014-2019
Light work: Studies into the mechanism of AAQ, a photoswitchable blocker voltage-gated K+ channels, led to discovery and development photochromic ligands that act at internal tetraethylammonium binding site (see picture). These molecules can be applied from extracellular side impart long-lasting photosensitivity on channels in living cells thereby afford photocontrol action potential firing neurons.
Photochromic channel blockers provide a conceptually simple and convenient way to modulate neuronal activity with light. We have recently described family of azobenzenes that function as tonic K(v) channels but require UV-A light unblock need be actively switched by toggling between two different wavelengths. now introduce red-shifted compounds fully operate in the visible region spectrum quickly turn themselves off dark. Furthermore, we developed version does not block effectively...
Rattling the cage: The two γ-aminobutyric acid (GABA) derivatives 1 and 2 exhibit efficient rapid (<5×10−6 s) GABA photorelease upon one-photon excitation combined with two-photon uncaging cross-section at λ=800 nm. Compounds were successfully used for release in intact brain tissue, thus offering attractive perspectives chemical neurosciences. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or...
Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet temporal dynamic range mechanism action acetylcholine (ACh) on modulation VTA circuits reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid precise optical manipulation nicotinic neurotransmission in living mice. We provide direct evidence that ACh tone fine-tunes firing properties DA...
Abstract Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related unrelated drug seeking consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated mice the impact of chronic on midbrain dopamine neuron activity its consequence trade-off between exploitation exploration. Model-based archetypal analysis revealed substantial inter-individual variability with passively...
Summary Social organization and division of labor are fundamental to animal societies, but how do these structures emerge from individual interactions, what role does neuromodulation play in shaping them? Using behavioral tracking a semi-natural environment, neural recordings, computational models integrating reinforcement social learning, we show that groups three isogenic mice spontaneously develop specialized roles while solving foraging task requiring decisions under constraints....
Ion channels are transmembrane proteins that control the movement of ions across cell membrane. They molecular machines make neurons excitable by enabling initiation and propagation action potentials. Rapid signaling within between requires complex processes couple sensing membrane voltage or neurotransmitter release to fast opening closing ion channel gate. Dysfunction an channel's gating module can have disastrous pathological consequences. However, linking changes modulation neural...
Optogenetics has become an emerging technique for neuroscience investigations owing to the great spatiotemporal precision and target selectivity it provides. Here we extend optogenetic strategy GABAA receptors (GABAARs), major mediators of inhibitory neurotransmission in brain. We generated a light-regulated receptor (LiGABAR) by conjugating photoswitchable tethered ligand (PTL) onto mutant containing cysteine-substituted α1-subunit. The installed PTL can be advanced or retracted from...
Licht am Steuer: Studien zum Mechanismus von AAQ, einem photoschaltbaren Blocker Kaliumkanälen, führten zur Entwicklung photochromer Liganden (oben im Bild), die mit der internen Tetraethylammonium-Bindungsstelle wechselwirken (unten). Diese Moleküle lassen sich Zelle außen applizieren und machen Kaliumkanäle in lebenden Zellen für lange Zeit lichtempfindlich, was es ermöglicht, das Feuern Neuronen zu steuern. Detailed facts of importance to specialist readers are published as ”Supporting...
Background and Purpose The photo‐isomerizable local anaesthetic, quaternary ammonium–azobenzene–quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans‐ QAQ blocks voltage‐gated K + Na channels silences action potentials pain‐sensing neurons. Upon photo‐isomerization to cis with near UV blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of trans not...
Glutamate is the major excitatory neurotransmitter in brain, and photochemical release of glutamate (or uncaging) a chemical technique widely used by biologists to interrogate its physiology. A basic prerequisite these optical probes bio-inertness before photolysis. However, all caged glutamates are known have strong antagonism toward receptors γ-aminobutyric acid, inhibitory transmitter. We developed probe that inert at concentrations effective for photolysis with violet light....
Abstract Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate network with and acetylcholine (ACh). In addition, VGLUT3-dependent increases ACh stores through synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients substance use disorders (SUDs) eating (EDs). mouse line generated understand neurochemical behavioral impact of p.T8I variant. VGLUT3 T8I/T8I male mice, signaling unchanged but synergy...
Nicotine intake is likely to result from a balance between the rewarding and aversive properties of drug, yet individual differences in neural activity that control aversion nicotine their adaptation during addiction process remain largely unknown. Using two-bottle choice experiment, we observed considerable heterogeneity nicotine-drinking profiles isogenic adult male mice, with about half mice persisting consumption even at high concentrations, whereas other stopped consuming. We found was...
Glutamate delta (GluD) receptors belong to the ionotropic glutamate receptor family, yet they don't bind and are considered orphan. Progress in defining ion channel function of GluDs neurons has been hindered by a lack pharmacological tools. Here, we used chemo-genetic approach engineer specific photo-reversible pharmacology GluD2 receptor. We incorporated cysteine mutation cavity located above putative pore, for site-specific conjugation with photoswitchable pore blocker. In constitutively...
Unter Bestrahlung setzen die γ-Aminobuttersäure(GABA)-Derivate 1 und 2 effizient schnell (<5×10−6 s) GABA frei, wobei Anregung durch ein oder zwei Photonen (λ=800 nm; mit außergewöhnlichem Einfangquerschnitt) erfolgen kann. Weil sich aus nach Zweiphotonenanregung auch in intaktem Hirngewebe freisetzen lässt, sind Verbindungen vielversprechend für Anwendungen den Neurowissenschaften. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents...