| Title: |
The ultrastructural properties of the endoplasmic reticulum govern microdomain signaling in perisynaptic astrocytic processes ; Les propriétés ultrastructurales du réticulum endoplasmique régissent la signalisation des microdomaines calciques dans les prolongements astrocytaires périsynaptiques. |
| Authors: |
Denizot, Audrey; Fernanda Veloz Castillo, María; Puchenkov, Pavel; Calì, Corrado; de Schutter, Erik |
| Contributors: |
Computational Neuroscience Unit Okinawa; Okinawa Institute of Science and Technology Graduate University (OIST); La pharmacologie des neurones et des astrocytes à l’aide des sciences du numérique (AISTROSIGHT); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Centre Hospitalier Lyon Sud CHU - HCL (CHLS); Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Theranexus Lyon -Centre Inria de Lyon; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria); Division of Biological and Environmental Sciences and Engineering; King Abdullah University of Science and Technology Thuwal, Saudi Arabia (KAUST); Scientific Computing and Data Analysis section, Research Support Division; Neuroscience Institute Cavalieri Ottolenghi Turin (NICO); Università degli studi di Torino = University of Turin (UNITO); Department of Neuroscience; This work was supported by a JSPS (Japan Society for the Promotion of Science) Standard Postdoctoral Fellowship for Research in Japan (21F21733). |
| Source: |
ISSN: 0894-1491. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2025 |
| Collection: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| Subject Terms: |
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
| Description: |
International audience ; Astrocytes recently emerged as key regulators of information processing in the brain. Ca2+ signals in perisynaptic astrocytic processes (PAPs) notably allow astrocytes to fine-tune neurotransmission at tripartite synapses. As most PAPs are below the diffraction limit, their content in Ca2+ stores and the contribution of the latter to astrocytic Ca2+ activity is unclear. Here, we reconstruct hippocampal tripartite synapses in 3D from a high resolution electron microscopy (EM) dataset and find that 75% of PAPs contain some endoplasmic reticulum (ER), a major astrocytic Ca2+ store. The ER in PAPs displays strikingly diverse shapes and intracellular spatial distributions. To investigate the causal relationship between each of these geometrical properties and the spatio-temporal characteristics of Ca2+ signals, we implemented an algorithm that generates 3D PAP meshes by altering the distribution of the ER independently from ER and cell shape. Reaction-diffusion simulations in these meshes reveal that astrocyte activity is governed by a complex interplay between the location of Ca2+ channels, ER surface-volume ratio and spatial distribution. In particular, our results suggest that ER-PM contact sites can act as local signal amplifiers if equipped with IP3R clusters but attenuate PAP Ca2+ activity in the absence of clustering. This study sheds new light on the ultrastructural basis of the diverse astrocytic Ca2+ microdomain signals and on the mechanisms that regulate neuron-astrocyte signal transmission at tripartite synapses. ; Les astrocytes sont des cellules jouant un rôle clé dans la régulation du traitement de l'information dans le cerveau. Les signaux calciques dans les prolongements astrocytaires périsynaptiques (PAP) permettent notamment aux astrocytes de réguler la neurotransmission au niveau des synapses tripartites. Comme la plupart des PAPs sont en dessous de la limite de diffraction, leur contenu en réserves de calcium et la contribution de ces derniers à l'activité calcique ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
BIORXIV: 2022.02.28.482292 |
| DOI: |
10.1002/glia.70091 |
| Availability: |
https://hal.science/hal-03591633; https://hal.science/hal-03591633v3/document; https://hal.science/hal-03591633v3/file/Denizotetal_2025.pdf; https://doi.org/10.1002/glia.70091 |
| Rights: |
https://hal.science/licences/copyright/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.2DDEB973 |
| Database: |
BASE |