Laurent Groc

Laurent Groc
Université Victor Segalen Bordeaux 2 | UB2 · Institut Interdisciplinaire de Neurosciences IINS

About

156
Publications
21,807
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
8,294
Citations
Citations since 2017
67 Research Items
4231 Citations
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Introduction

Publications

Publications (156)
Article
Full-text available
We provide evidence of a local synaptic nanoenvironment in the brain extracellular space (ECS) lying within 500 nm of postsynaptic densities. To reveal this brain compartment, we developed a correlative imaging approach dedicated to thick brain tissue based on single-particle tracking of individual fluorescent single wall carbon nanotubes (SWCNTs)...
Preprint
Full-text available
Specific autoantibodies against the NMDA-receptor (NMDAR) GluN1 subunit cause severe and debilitating NMDAR-encephalitis. Autoantibodies induce prototypic disease symptoms resembling schizophrenia, including psychosis and cognitive dysfunction. Using a mouse passive transfer model applying human monoclonal anti-GluN1-autoantibodies, we observed CA1...
Article
Full-text available
Single molecule localization (SML) and tracking (SPT) techniques, such as (spt)PALM, (u/DNA)PAINT and quantum dot tracking, have given unprecedented insight into the nanoscale molecular organization and dynamics in living cells. They allow monitoring individual proteins with millisecond temporal resolution and high spatial resolution (<30 nm) by pr...
Article
Full-text available
Shank3 monogenic mutations lead to autism spectrum disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95–GKAP–Shank3–Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic...
Preprint
Full-text available
We provide evidence of a local synaptic nano-environment in the brain extracellular space (ECS) lying within 500 nm of postsynaptic densities. To reveal this brain compartment, we developed a correlative imaging approach dedicated to thick brain tissue based on single-particle tracking of individual fluorescent single wall carbon nanotubes (SWCNTs)...
Article
Full-text available
A dysfunction of the glutamatergic transmission, especially of the NMDA receptor (NMDAR), constitutes one of the main biological substrate of psychotic disorders, such as schizophrenia. The NMDAR signaling hypofunction, through genetic and/or environmental insults, would cause a neurodevelopmental myriad of molecular, cellular, and network alterati...
Article
Proteasome activity at the excitatory synapse plays an important role in neuronal communication. The proteasome translocation to synapses is mediated by neuronal activity, in particular the activation of N-methyl-d-aspartate receptors (NMDARs). These receptors are composed of different subunits with distinct trafficking properties that provide vari...
Chapter
Neuronal communication mostly relies on a constant adjustment of the number and subtype of neurotransmitter receptors and ion channels at the plasma membrane. Although classical fluorescence ensemble approaches have provided valuable insights into cellular and molecular pathways, their inherent limitations (e.g., average behaviors, spatial resoluti...
Article
Full-text available
N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signalling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whethe...
Article
Full-text available
Fluorescent nanoparticles dedicated to bioimaging applications should possess specific properties that have to be maintained in the aqueous, reactive, and crowded biological environment. These include chemical and photostability, small size (on the scale of subcellular structures), biocompatibility, high brightness, and good solubility. The latter...
Article
Full-text available
Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that...
Article
Luminescent single wall carbon nanotubes are now well established, as unique nanoreporters to probe the brain extracellular space[1]. On the imaging side, this comes from their rich near-infrared optical properties, which also eventually be improved by sp ³ -chemical functionalization[2]. In addition, their uncommon 1D morphology is an important as...
Article
Full-text available
The γ-aminobutyric acid type A receptor (GABAAR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GAB...
Article
NMDA receptors are ligand-gated ion channels that are found throughout the brain and are required for both brain development and many higher order functions. A variety of human patients with diverse clinical phenotypes have been identified that carry autoantibodies directed against NMDA receptor subunits. Here we focus on two general classes of aut...
Article
Key points: NMDA receptors expressed by dopamine neurons of the ventral tegmental area (VTA) play a central role in glutamate synapse plasticity, neuronal firing and adaptative behaviours. The NMDAR surface dynamics shape synaptic adaptation in hippocampal networks, as well as associative memory. We investigated the basic properties and role of th...
Preprint
Full-text available
Shank3 monogenic mutations lead to Autism Spectrum Disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic...
Preprint
Full-text available
Transient information input to brain leads to persistent changes in synaptic circuit, thereby forming memory engrams. Synapse undergoes coordinated functional and structural changes during this process but how such changes are achieved by its component molecules still largely remain enigmatic. We found that activated CaMKII, the central player of s...
Article
Full-text available
Background When psychosis develops in NMDAR antibody encephalitis it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their role in psychosis onset and response to ant...
Article
Full-text available
Significance Glutamatergic synapses onto pyramidal neurons are diverse in shape, size, and NMDAR-dependent long-term plasticity according to their dendritic location, i.e., proximal or distal to the soma. Deciphering the fine organization of NMDAR subtypes along the dendritic arbor of hippocampal neurons is key to understand the functional diversit...
Preprint
Full-text available
Background α-Synuclein misfolding and aggregation contribute to synaptic dysfunction in synucleinopathies, including Parkinson’s disease. However, the mechanism underlying the effect of α-synuclein on synaptic components remains unclear. Since the N-methyl-D-aspartic acid receptor (NMDAR) plays a key role in glutamate synapse pathophysiology, we he...
Article
Full-text available
In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult mice under degenerative conditions. Using electro...
Article
Luminescent single wall carbon nanotubes are now well established, as unique nanoreporters to probe the brain extracellular space[1-3]. On the imaging side, this comes from their rich near-infrared optical properties, which also eventually be improved by sp ³ -chemical functionalization. In addition, their uncommon 1D morphology is an important ass...
Article
The brain is a highly dynamic structure with the extracellular space taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the extracellular space, which constitutes a key microenvironment for cellular communication and clearance of toxic metabolites. Nevertheless, the extracellular space has no...
Article
Full-text available
Cellular and tissue imaging in the second near-infrared window (NIR-II, ~1000–1350 nm) is advantageous for in vivo studies because of low light extinction by biological constituents at these wavelengths. However, deep tissue imaging at the single molecule sensitivity has not been achieved in the NIR-II window due to lack of suitable bio-probes. Sin...
Article
There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although th...
Preprint
Full-text available
N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signaling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether...
Article
Full-text available
Circulating autoantibodies directed against extracellular domains of the glutamatergic N-methyl-D-aspartate receptors (NMDAR-Ab) elicit psychotic symptoms in humans and behavioral deficits in animal models. Recent advances suggest that NMDAR-Ab exert their pathogenic action by altering the trafficking of NMDAR, which results in a synaptic NMDAR hyp...
Article
Full-text available
Astrocytes constantly adapt their ramified morphology in order to support brain cell assemblies. Such plasticity is partly mediated by ion and water fluxes, which rely on the water channel aquaporin-4 (AQP4). The mechanism by which this channel locally contributes to process dynamics has remained elusive. Using a combination of single-molecule and...
Preprint
Cellular and tissue imaging in the second near-infrared window (NIR-II, ~1000 - 1350 nm) is advantageous for in vivo studies because of low light extinction by biological constituents at these wavelengths. However, deep tissue imaging at the single molecule sensitivity has not been achieved in the NIR-II window due to lack of suitable bio-probes. S...
Article
Full-text available
Through the formation of fluorescent self-interference (SELFI), quantitative intensity and phase imaging enables the 3D localization of single fluorescent molecules inside a fixed tissue with an accuracy well-beyond the diffraction limit. Here we demonstrate that this concept can be extended to 3D super-resolution microscopy and 3D single particle...
Article
Over the last decade, developments in single molecule imaging have changed our vision of synaptic physiology. By providing high spatio-temporal resolution maps of the molecular actors of neurotransmissions, these techniques have revealed that pre- and post-synaptic proteins are not randomly distributed but precisely organized at the nanoscale, and...
Article
The brain extracellular space (ECS) is a system of narrow compartments whose intricate nanometric structure has remained elusive until very recently. Understanding such a complex organisation represents a technological challenge that requires a technique able to resolve these nanoscopic spaces and simultaneously characterize their rheological prope...
Article
NMDA receptors (NMDARs) play key roles in the use-dependent adaptation of glutamatergic synapses underpinning memory formation. In the forebrain, these plastic processes involve the varied contributions of GluN2A- and GluN2B-containing NMDARs that have different signaling properties. Although the molecular machinery of synaptic NMDAR trafficking ha...
Article
Full-text available
Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement 1 . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cel...
Article
Recent years have seen a flourishing literature on detection of circulating autoantibodies against neurotransmitter receptors in patients with neuropsychiatric disorders. These studies have generated hope for a better understanding of the underlying molecular dysfunctions and for appropriate therapeutic strategies. However, the detection of these a...
Article
Background: Over the past decade, an increasing number of neurological and neuropsychiatric diseases have been associated with the expression of autoantibodies directed against neuronal targets, including neurotransmitter receptors. Although cell-based assays are routinely used in clinics to detect the presence of immunoglobulins, such tests often...
Chapter
The spatiotemporal organization of neurotransmitter receptors within synapses is a critical determinant of synaptic transmission and adaptation, and thus of information processing and storage in the brain. Long considered as immobile at the plasma membrane, glutamate ionotropic receptors—the principal mediators of fast excitatory neurotransmission—...
Article
Luminescent single-walled carbon nanotubes (SWCNTs) are unique nanoemitters that allow near-infrared single molecule detection within biological tissues. Interestingly, the recent discovery of up-conversion luminescence from (6,5) SWCNTs provides a novel opportunity for deep tissue single SWCNT detection. Yet, the optimal excitation strategy for vi...
Article
Full-text available
Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway under...
Article
Full-text available
Animal models are essential tools for basic pathophysiological research as well as validation of therapeutic strategies for curing human diseases. However, technical difficulties associated with classical transgenesis approaches in rodent species higher than mus musculus have prevented this long-awaited development. The availability of viral-mediat...
Article
Full-text available
Cortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype...
Article
Full-text available
The identification of circulating autoantibodies against neuronal receptors in neuropsychiatric disorders has fostered new conceptual and clinical frameworks. However, detection reliability, putative presence in different diseases and in health have raised questions about potential pathogenic mechanism mediated by autoantibodies. Using a combinatio...
Article
Full-text available
Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synapt...
Article
Full-text available
Circulating autoantibodies against glutamatergic N-methyl-D-aspartate receptor (NMDAR-Ab) have been reported in a proportion of patients with psychotic disorders, raising hopes for more appropriate treatment for these antibody-positive patients. However, the prevalence of circulating NMDAR-Ab in psychotic disorders remains controversial with detect...
Data
D-serine and glycine dose-response curves. Summary of Hill coefficient (nH), half maximal concentration (EC50) and n-values for the glycine/D-serine dose-response curves obtained on GluN2A- and GluN2B-NMDARs recombinants. p-Values (unpaired, two-tailed Student t-test) assess the difference between the EC50 obtained with D-serine and glycine. DOI: h...
Data
Co-agonist and NMDAR-subunit developmental switch. Summary of the effects of BsGO, RgDAAO, Ro25-6981 and zinc normalized to baseline (mean ± s.e.m) in slices obtained from rats at indicated ages (see Figure 5—figure supplement 1). n values are indicated as well as p-values (paired Student t-test) assessing the significance of the effect achieved co...
Data
Capillary electrophoresis measurements. Summary of the measurements of glutamate, glycine and D-serine content in slices at different ages. Values indicate average content (in nmoles per mg of tissue) ± s.e.m. p-Values indicate the level of significance (student t-test) between values in <P10 slices compared to values in adults. DOI: http://dx.doi....
Article
The subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content of GluN2A- and GluN2B-containing receptors, greatly influences the glutamate synaptic transmission. Receptor co-agonists, glycine and D-serine, have intriguingly emerged as potential regulators of the receptor trafficking in addition to their requirement for it...
Article
The Second International Workshop on Human Endogenous Retroviruses and Disease, Washington DC, March 13–14 2017 brought together international basic and clinical scientists investigating the involvement of human endogenous retroviruses (HERVs) in complex human diseases.
Article
Full-text available
Today, the main problem of the so-called autoimmune psychosis is that patients are not diagnosed. In order to help the physician to evocate it and to consider an autoantibody screening, we propose to gather elements enabling to build a risk score for autoimmune psychosis. This score should take into account the personal and/or familial history of e...
Article
Full-text available
Schizophrenia and bipolar disorder are neuropsychiatric disorders of unknown origin. It seems that these two disorders share some common etiopathogenic mechanisms including genetic, environmental and inflammatory ones. Reactivation of the human endogenous retrovirus type W (HERV-W) can be a shared element in the pathophysiology of schizophrenia and...
Article
Full-text available
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are invol...
Article
Full-text available
Astrocytes, the major glial cell type in the central nervous system (CNS), are critical for brain function and have been implicated in various disorders of the central nervous system. These cells are involved in a wide range of cerebral processes including brain metabolism, control of central blood flow, ionic homeostasis, fine-tuning synaptic tran...
Article
Full-text available
Background The diagnostic scheme for psychiatric disorders is currently based purely on descriptive nomenclature given that biomarkers subtypes and clearly defined causal mechanisms are lacking for the vast majority of disorders. The emerging field of “immuno-psychiatry” has the potential to widen the exploration of a mechanism-based nosology, poss...
Article
The brain is a dynamic structure with the extracellular space (ECS) taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the ECS, which constitutes a key microenvironment for cellular communication and the clearance of toxic metabolites. The spatial organization of the ECS varies during sleep,...
Article
Full-text available
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with a...
Article
Full-text available
Objective: To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. Methods: We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encepha...
Article
Full-text available
Objectives: It is unknown whether a cytokine signature may help the identification of subgroup of patient who would respond to personalized treatment. As interleukin-1 beta (Il-1β) seems to play a major role in mood disorder, a systematic review and meta-analysis of its potential role in major depressive disorder (MDD) was carried out. Methods:...