2. Academic Validation
  3. Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices

Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices

  • Nat Commun. 2024 Jun 26;15(1):5402. doi: 10.1038/s41467-024-49773-1.
Péter Berki # 1 2 3,  Csaba Cserép # 4,  Zsuzsanna Környei # 4,  Balázs Pósfai 4,  Eszter Szabadits 4,  Andor Domonkos 4 5,  Anna Kellermayer 4,  Miklós Nyerges 4,  Xiaofei Wei 6,  Istvan Mody 6,  Araki Kunihiko 7 8,  Heinz Beck 7 8,  He Kaikai 9,  Wang Ya 10,  Nikolett Lénárt 4,  Zhaofa Wu 11,  Miao Jing 10,  Yulong Li 9,  Attila I Gulyás 2,  Ádám Dénes 12
Affiliations

Affiliations

  • 1 János Szentágothai Doctoral School of Neuroscience, Semmelweis University, Budapest, H-1083, Hungary.
  • 2 Laboratory of Cerebral Cortex Research, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary.
  • 3 Laboratory of Neuronal Network and Behaviour, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary.
  • 4 Momentum Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary.
  • 5 Laboratory of Thalamus Research, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary.
  • 6 Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
  • 7 Institute of Experimental Epileptology and Cognition Research, Medical University of Bonn, Bonn, 53127, Germany.
  • 8 University Hospital Bonn, Bonn, Germany.
  • 9 State Key Laboratory of Membrane Biology, New Cornerstone Science Laboratory, School of Life Sciences, Peking University, 100871, Beijing, China.
  • 10 Chinese Institute for Brain Research, 102206, Beijing, China.
  • 11 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.
  • 12 Momentum Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary. denes.adam@koki.hu.
  • # Contributed equally.
PMID: 38926390 DOI: 10.1038/s41467-024-49773-1
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.

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