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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1456974
This article is part of the Research Topic 15 Years of Frontiers in Cellular Neuroscience: Microglia Origin and Phenotype Diversity View all 3 articles

Time-dependent phenotypical changes of microglia drive alterations in hippocampal synaptic transmission in acute slices

Provisionally accepted
Laura Ferrucci Laura Ferrucci 1Bernadette Basilico Bernadette Basilico 1,2Ingrid Reverte Ingrid Reverte 1,3Francesca Pagani Francesca Pagani 1Giorgia Scaringi Giorgia Scaringi 1,2Federica Cordella Federica Cordella 1,2Barbara Cortese Barbara Cortese 4Gaia De Propris Gaia De Propris 1Andrea Galeone Andrea Galeone 1Letizia Mazzarella Letizia Mazzarella 1Alessandro Mormino Alessandro Mormino 1Stefano Garofalo Stefano Garofalo 1Azka Khan Azka Khan 1Valeria de Turris Valeria de Turris 2Paola Bezzi Paola Bezzi 1,5Cornelius Gross Cornelius Gross 6Daniele Caprioli Daniele Caprioli 1,3Cristina Limatola Cristina Limatola 1,7Silvia Di Angelantonio Silvia Di Angelantonio 1,2Davide Ragozzino Davide Ragozzino 1,3*
  • 1 Department of Physiology and Pharmacology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy
  • 2 Center for Life NanoScience, Italian Institute of Technology (IIT), Rome, Italy
  • 3 Santa Lucia Foundation (IRCCS), Rome, Lazio, Italy
  • 4 National Research Council-Nanotechnology Institute (CNR Nanotec), 00185, Rome, Italy, Roma, Italy
  • 5 Département des Neurosciences Fondamentales, Faculté de Biologie et de Médecine, Université de Lausanne, Lausanne, Switzerland
  • 6 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
  • 7 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy, Pozzilli, Italy

The final, formatted version of the article will be published soon.

    It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding the role of microglia in synaptic regulation is derived from studies in acute brain slices. However, it is still uncertain to what extent the preparation and maintenance of acute slices can influence microglial function and whether microglial changes may affect synaptic transmission. In this study, we examined the impact of acute slice resting time on hippocampal CA1 microglia, by assessing morphological and functional parameters at two distinct time intervals. We report that after four hours from slicing microglia undergo morphological, functional, and transcriptional changes, including a decrease in the number of branches and in their movement speed. Furthermore, microglia acquire a reactive phenotype, characterized by increased amplitude of outward rectifying K+ currents, increased expression of the pro-inflammatory cytokine Tnf-α and altered expression of the microglial receptors Cx3cr1 and P2y12r. We also examined time-dependent changes of excitatory synaptic transmission in CA1 pyramidal neurons from acute hippocampal slices, reporting time-dependent decrease in both amplitude and frequency of postsynaptic currents (sEPSCs), along with a decrease in spine density. Noticeably, sEPSCs amplitude decrease was absent in slices prepared from PLX 5622 microglia-depleted mice, suggesting that this time-dependent effect on synaptic transmission is microglia-dependent. Our findings highlight possible causal relation between microglia phenotypic changes in the hours following slice preparation and concomitant synaptic changes, pointing to the mechanisms of acute synaptic modulation, whose understanding is crucial for unraveling microglia-neurons interplay in nature. Furthermore, they emphasize the potential issues associated with experimental time windows in ex vivo samples.

    Keywords: Microglia, acute slices, Synaptic Transmission, Microglia Reactivity, Electrophysiology

    Received: 29 Jun 2024; Accepted: 09 Oct 2024.

    Copyright: © 2024 Ferrucci, Basilico, Reverte, Pagani, Scaringi, Cordella, Cortese, De Propris, Galeone, Mazzarella, Mormino, Garofalo, Khan, de Turris, Bezzi, Gross, Caprioli, Limatola, Di Angelantonio and Ragozzino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Davide Ragozzino, Department of Physiology and Pharmacology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy

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