Search results for "Synapse"

Neuronal Activity Patterns in the Developing Barrel Cortex

2017

International audience; The developing barrel cortex reveals a rich repertoire of neuronal activity patterns, which have been also found in other sensory neocortical areas and in other species including the somatosensory cortex of preterm human infants. The earliest stage is characterized by asyn-chronous, sparse single-cell firing at low frequencies. During the second stage neurons show correlated firing, which is initially mediated by electrical synapses and subsequently transforms into network bursts depending on chemical synapses. Activity patterns during this second stage are synchronous plateau assemblies, delta waves, spindle bursts and early gamma oscillations (EGOs). In newborn rod…

2017

Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome, autism spectrum disorder (ASD), and intellectual disability. Although, a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the post-synaptic protein scaffold, the molecular processes at synapses of individuals harboring SHANK3 mutations are still far from being understood. In this study, we biochemically isolated the post-synaptic density (PSD) fraction from striatum and hippocampus of adult Shank3Δ11-/- mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteo…

Visual Working Memory Requires Permissive and Instructive NO/cGMP Signaling at Presynapses in the Drosophila Central Brain.

2017

The gaseous second messenger nitric oxide (NO) has been shown to regulate memory formation by activating retrograde signaling cascades from post- to presynapse that involve cyclic guanosine monophosphate (cGMP) production to induce synaptic plasticity and transcriptional changes. In this study, we analyzed the role of NO in the formation of a visual working memory that lasts only a few seconds. This memory is encoded in a subset of ring neurons that form the ellipsoid body in the Drosophila brain. Using genetic and pharmacological manipulations, we show that NO signaling is required for cGMP-mediated CREB activation, leading to the expression of competence factors like the synaptic homer pr…

Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma

2018

Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells. Particularly, the IS displaying a T cell receptor-rich (TCR-rich) central…

Transient Confinement of CaV2.1 Ca2+-Channel Splice Variants Shapes Synaptic Short-Term Plasticity

2019

Summary The precision and reliability of synaptic information transfer depend on the molecular organization of voltage-gated calcium channels (VGCCs) within the presynaptic membrane. Alternative splicing of exon 47 affects the C-terminal structure of VGCCs and their affinity to intracellular partners and synaptic vesicles (SVs). We show that hippocampal synapses expressing VGCCs either with exon 47 (CaV2.1+47) or without (CaV2.1Δ47) differ in release probability and short-term plasticity. Tracking single channels revealed transient visits (∼100 ms) of presynaptic VGCCs in nanodomains (∼80 nm) that were controlled by neuronal network activity. Surprisingly, despite harboring prominent bindin…

Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities

2021

Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular lev…

Disruption of otoferlin alters the mode of exocytosis at the mouse inner hair cell ribbon synapse

2019

Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C-2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from f…

Astrocytic Ephrin-B1 Controls Synapse Formation in the Hippocampus During Learning and Memory

2020

Astrocytes play a fundamental role in synapse formation, pruning, and plasticity, which are associated with learning and memory. However, the role of astrocytes in learning and memory is still largely unknown. Our previous study showed that astrocyte-specific ephrin-B1 knock-out (KO) enhanced but ephrin-B1 overexpression (OE) in hippocampal astrocytes impaired contextual memory recall following fear conditioning. The goal of this study was to understand the mechanism by which astrocytic ephrin-B1 influences learning; specifically, learning-induced remodeling of synapses and dendritic spines in CA1 hippocampus using fear-conditioning paradigm. While we found a higher dendritic spine density …

Nitric oxide/cGMP signaling via guanylyl cyclase isoform 1 modulates glutamate and GABA release in somatosensory cortex of mice

2017

Abstract In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input–output curves of evoked signa…

The stressed cytoskeleton: How actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior

2015

Stress alters synaptic plasticity but the molecular and cellular mechanisms through which environmental stimuli modulate synaptic function remain to be elucidated. Actin filaments are the major structural component of synapses and their rearrangements by actin-binding proteins (ABPs) are critical for fine-tuning synaptic plasticity. Accumulating evidence suggests that some ABPs are specifically regulated by stress and stress-related effectors such as glucocorticoids and corticotropin releasing hormone. ABPs may thus be central in stress-induced perturbations at the level of synaptic plasticity, leading to impairments in behavioral domains including cognitive performance and social behavior.…