Search results for "apse"

Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication.

2020

Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous. For example, presynaptic voltage-gated calcium channels (VGCCs) and postsynaptic ligand-gated ion channels such as AMPA receptors (AMPARs) are organized into so-called nanodomains where individual molecules are only transiently trapped. These pre- and postsynaptic nanodomains are characterized by a high density of molecules but differ in their molecular organization an…

Modulation of information processing by AMPA receptor auxiliary subunits

2020

AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate…

To invade, or to observe, that is the question

2018

TCR signalling network organization at the immunological synapses of murine regulatory T cells.

2017

Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in Treg cells and Tconv cells. With the exception of Themis which we detected in lower amounts in Treg cells, other major TCR signalling components were found equally abundant, however, their phosphorylation-status notably discriminates Treg cells from Tconv cells. Overall, this s…

Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior

2021

Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses…

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…

Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation

2018

Somatic stem cells have been identified in multiple adult tissues. Whether self-renewal occurs symmetrically or asymmetrically is key to understanding long-term stem cell maintenance and generation of progeny for cell replacement. In the adult mouse brain, neural stem cells (NSCs) (B1 cells) are retained in the walls of the lateral ventricles (ventricular-subventricular zone [V-SVZ]). The mechanism of B1 cell retention into adulthood for lifelong neurogenesis is unknown. Using multiple clonal labeling techniques, we show that the vast majority of B1 cells divide symmetrically. Whereas 20%-30% symmetrically self-renew and can remain in the niche for several months before generating neurons, …