Berki, Péter and Cserép, Csaba and Környei, Zsuzsanna and Pósfai, Balázs and Cserépné Szabadits, Eszter and Domonkos, Andor and Kellermayer, Anna and Nyerges, Miklós and Wei, Xiaofei and Mody, Istvan and Kunihiko, Araki and Beck, Heinz and Kaikai, He and Ya, Wang and Lénárt, Nikolett and Wu, Zhaofa and Jing, Miao and Li, Yulong and Gulyás, Attila and Dénes, Ádám (2024) Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices. NATURE COMMUNICATIONS, 15 (1). ISSN 2041-1723
|
Text
s41467-024-49773-1.pdf - Published Version Available under License Creative Commons Attribution. Download (14MB) | Preview |
Abstract
Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.
Item Type: | Article |
---|---|
Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 24 Sep 2024 08:23 |
Last Modified: | 24 Sep 2024 08:23 |
URI: | https://real.mtak.hu/id/eprint/205615 |
Actions (login required)
![]() |
Edit Item |