Long-term potentiation

Understanding the fine-scale connectivity structure of neural networks is key to deciphering their behaviour. Motifs in network connectivity are instrumental in relating circuit structure to dynamical properties of neural activity, such as covariability and dimensionality [1]. Experiments have made significant progress in measuring precise neural connectivity: multi-patch experiments, as well as more recent studies in connectomics, have found that certain types of three-neuron (triplet) connectivity motifs are over- or underrepresented relative to chance (Fig.1A, [2,3]). However, it is still u

Among the brain structures affected in Schizophrenia is the hippocampus. In addition to structural changes [1], dysfunctions of the synaptic plasticity have also been observed supporting cognitive impairment [2]. To study these phenomena in depth, we aim to develop and match two models of the pathology, computational and experimental. Our work is based on an existing computational hippocampus model [3] and a 3-hits mouse model [4]. For that purpose, we analyze electrophysiological signals recorded with Multi-Electrode Array (MEA) on hippocampal slices to extract synaptic transmission character

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses, can be subdivided into two mechanistically different forms of NMDAR-dependent synaptic potentiation based on their independence of (LTP1) or dependence on (LTP2) de novo protein synthesis (PS). Previous experiments reported the requirement of CP-AMPAR activation and intracellular calcium stores for LTP2 but not LTP11,2. Here the requirement for CP-AMPARs and intracellular calcium stores in structural LTP (sLTP) were investigated. Simultaneous field potential recordings and two-photon imaging were carried out in acute hippocampal sli

Acute stress exposures are the building blocks of chronic stress. Unravelling the mechanisms underpinning the whole-body response to acute stress is critical to understand this neglected aspect of health and disease. A single acute stress exposure rapidly modulates gut-brain axis signalling including intestinal permeability and hippocampal plasticity. The gut microbiota is increasingly recognized as an important modulator of mood and cognition, and microbially-produced metabolites such as butyrate can be a key regulator of brain and gut function via the gut-brain axis. The aim of this work is

…in CA1, alterations of both long-term potentiation and dendritic spines’ structure. At behavioral level, RNF10 downregulation suppres

…in the cellular mechanisms underlying long-term potentiation (LTP) and memory. Because a decrease of cNs is observed in aging and neurodegenerative disorders, including Alzheimer's Disease (AD), drugs restoring cNs levels, such as PDE inhibitors (PDE-Is), have been proposed as potential therapeutic strategies. Previous studies showed a crosstalk between cNs and amyloid-beta (Aβ), a peptide extensively known for its pathological role in AD but also implicated in the physiological processes of synaptic plasticity and memory.Based on these f

Theta oscillations (4-12 Hz) in the hippocampus are caused by the synchronous bursting activity of neuronal populations. They are critical for grouping and selecting neuronal ensembles in the context of spatial navigation, memory, and learning, but the reason why this frequency band is particularly effective for adjusting neuronal ensembles remains speculative. Here we show that burst activity at the CA3-CA1 synapse of the mouse hippocampus leads to a rapid activation of astrocytic leaflets possibly via the retrograde release of endocannabinoids that activate transient receptor potential chann

The medial prefrontal cortex (mPFC) is involved in cognitive and emotional functions housing neurons and astrocytes, impacting mPFC activity. To this end, astrocytes express several GPCR to fine-tune synaptic transmission such as CB1R and adenosine A1 and A2A receptors (A1R, A2AR). Since interactions of these receptors in astrocytes are not known, this work aims to fill the gap of the crosstalk between CB1R and adenosine receptors and their contribution for mPFC synaptic plasticity.CB1R-A1R and CB1R-A2AR complexes were observed in primary cultures of astrocytes, by using Proximation Ligation a

Pleiotropic cytokine IL-6 regulates various processes in the body including neuronal functions. IL-6 can signal through its membrane bound receptor IL-6R, which associates with IL-6 signal transducer gp130 IL-6st/gp130 (classical signaling), or binds to soluble IL-6R to act on any cell that that expresses IL-6st/gp130 (trans-signaling). Alzheimer’s disease related enzyme BACE1 has critically important roles in synaptic function and cleaves IL-6st/gp130 as well as IL-6R.Therefore, we hypothesize that BACE1 could be essential for the alteration of neuron excitability and synaptic plasticity via

Background: Radiotherapy is a common treatment for brain tumors, yet it often leads to cognitive decline. Past understanding suggested this damage was irreversible due to DNA damage and cell death. However, recent studies propose that it may be reversible, as it affects active cells. Scientists focus on hippocampal activity, crucial for learning and memory, to explore this. Radiation is thought to decrease neurogenesis and increase neuroinflammation in the hippocampus. Anti-inflammatory drugs are suggested as a potential solution to mitigate cognitive decline from radiation.Aims: Analyzing the

In this work, we want to dissect the specific and sex-dependent role of CB1 signalling in different cell types and its impact on hippocampal functions such as navigation or memory. A specific Cre-mediated CB1 deletion on neurons (excitatory and inhibitory), astrocytes, or interneurons in CB1-flox males and females was performed. Viral vectors (AAV-Cre) were injected bilaterally into the hippocampus of these mice. The Barnes maze was used for learning, memory, navigation and the Novel Object Recognition Test (NORT) for recognition memory. Anxiety-like behavioural protocols were also performed b

While dissociated cultures of rodent neurons on microelectrode arrays (MEAs) have become a prominent method for studying neuronal network properties, establishing human neuronal cultures with mature electrophysiological features compatible with MEAs has posed a significant challenge. The aim of this study was to establish a reliable protocol for generating human-derived neuronal networks on High Density Microelectrode Arrays (HD-MEA) and to characterize their electrophysiological features for potential applications in disease modeling and therapeutic testing. Human-induced pluripotent stem cel

Activation of microglia by inflammation or chronic disease has profound effects on neurons and synapses. The details of this communication between the immune system and the brain are under active investigation. Common strategies to activate microglia, such as lipopolysaccharide injection or experimental autoimmune encephalomyelitis (EAE) primarily activate the peripheral immune system, triggering a complex and protracted response of the whole organism. In order to activate microglia selectively and with precise timing, we used chemogenetic activation of a Gq-DREADD expressed exclusively in mic

The stress response is a significant precipitating factor in various psychiatric disorders. Numerous neuropsychiatric disorders are characterized by sex differences in the prevalence, type, and severity of symptoms, which include cognitive dysfunctions mainly supported by the prefrontal cortex (PFC). This study aims to evaluate the sexual dimorphic effects of acute stress on PFC synaptic properties, as well as on both the intrinsic and synaptic properties of PFC-basolateral amygdala (BLA) and PFC-PFC projection neurons. Adult male and female mice were exposed to either restraint stress (RS) or

Hippocampal Interneurons are heavily myelinated but show differences in composition/distribution and myelin function. Contactin-2 (CNTN2 or TAG-1), an adhesion molecule of the immunoglobulin superfamily, expressed in glia and axons, organizes the juxtaparanodal region of myelinated fibers and clusters voltage-gated potassium channels under the myelin sheath. CNTN2 has a dynamic spatial and temporal expression and is implicated in migration during development as well as in neuropathology (multiple sclerosis, AD). We have shown that a significant population of hippocampal GABAergic interneurons

Aim: Motor learning significantly impacts daily life, triggering notable changes in the primary motor cortex (M1) and basal ganglia (BG). Dopamine (DA) mediates these changes, with Darpp-32 playing a key role in DA transmission. Although extensively studied in the BG's striatum, Darpp-32's function in the motor cortex remains largely unexplored. This study aims to characterize Darpp-32 in motor cortices, examining cellular expression and its impact on motor behavior, synaptic and structural plasticity.Methods: Anatomical study: Using C57BL/6 mice, we examined Darpp-32 distribution across corti

…during this time have been linked to long-term effects on cognition. The brain undergoes significant remodelling involving dendritic arborization, synaptogenesis and neuron proliferation within and between areas, particularly in the hippocampus, which plays a vital role in spatial memory processing. Spatial memory processing ability continues to develop alongside hippocampal maturation particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is essential for activity

GRIN disorders are rare neurodevelopmental disorders caused by pathogenic variants in the GRIN genes that encode the N-methyl-D-aspartate receptor (NMDAR) subunits. Two such missense variants of the GluN1 subunit, GRIN1-G620R and GRIN1-G827R, have been identified in multiple patients with profound intellectual disability and developmental delay. To understand the nature of the NMDAR deficits imparted by these variants, we generated Grin1 G620R and G827R mouse models that mimic the heterozygous condition found in affected individuals. Synaptic function was assessed using electrophysiological re

The dentate gyrus (DG) serves as an information gateway to the hippocampal formation. It receives sensory information from entorhinal cortex via perforant path (PP) and can be subdivided into parts including a supra- and an infrapyramidal blade. Typically, synaptic plasticity within the DG has mostly been examined in the suprapyramidal blade, whereas little is known about the extent to which synaptic plasticity is expressed and maintained in the infrapyramidal blade.This study compared synaptic plasticity in both blades of the DG that was evoked by patterned electrophysiological stimulation of

…investigated deficits in hippocampal long-term potentiation/depotentiation changes in the sub-chronic phencyclidine (scPCP) rat model for schizophrenia and how chronic exercise as a non-pharmacological treatment may produce hippocampal synaptic and cognitive improvements.Methods: 60 Female Lister Hooded rats (50 for acute recording and 10 for chronic recording) were dosed with either saline or PCP (2 mg/kg, i.p.) twice daily for seven days foll

…a single dose of cocaine, leading to long-term potentiation. Gene expression and synaptic activity are reported to recover within the first 24 hours post cocaine exposure, but a memory of the first insult is thought to prevail, as a second exposure leads to more expansive activation. To gain mechanistic insights into the chromatin structure alterations seen by 24h and understand the cascade of events that disturbs networks of regulatory sequences and genes, we

N6-methyladenosine (m6A) methylation, the most prevalent eukaryotic mRNA modification, is enriched in the mammalian brain and the synaptic transcriptome. m6A methylation is dynamically regulated by enzymes called m6A writers (METTL3/14) and erasers (FTO), that are present in distal neuronal processes. Although recent studies link dynamic m6A methylome changes during synaptic plasticity to memory consolidation, the exact mechanisms in neuronal circuits remain unclear. This study investigates m6A methylation effects on synaptic transmission and plasticity within hippocampal networks, utilizing p

The G-protein coupled receptor GABAB is an important regulator of presynaptic neurotransmitter release and postsynaptic excitability. In anti-GABABR autoimmune encephalitis pathogenic autoantibodies (aAB) target the GABAB receptor, leading to various symptoms, including epilepsy, cognitive disorders, and short-term memory loss. Here we aimed at evaluating the influence of these aAB on hippocampal-dependent cognitive and epileptic pathways. We used purified patient-derived antibodies (control- and anti-GABABR-IgG) in a chronic mouse model of the disease to evaluate the memory formation via Nove

Aims: This study aims to elucidate the transcriptomic changes underlying thalamic alterations in an animal model of schizophrenia. Methods: We used a 'dual hit' rat model of schizophrenia, which combines an injection of non-competitive NMDA receptor antagonist MK-801 at P7 and 8 weeks of postweaning social isolation. The model was developed in both male and female rats. At 3 months, behavioral tests and RNA sequencing (RNAseq) of the thalamus were performed. Differential expressed genes (DEGs) and enriched categories were validated in silico via MAGMA using GWAS summary statistics of the Psych