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Microglia modulate TNFα-mediated synaptic plasticity.

Dimitrios Kleidonas1,2,3, Matthias Kirsch1,4, Geoffroy Andrieux5

  • 1Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Glia
|May 20, 2023
PubMed
Summary
This summary is machine-generated.

Tumor necrosis factor α (TNFα) affects neuronal plasticity. Pro-inflammatory microglia help maintain synaptic stability by regulating excitatory and inhibitory neurotransmission, acting as gatekeepers of synaptic change.

Keywords:
GluA1TNFαexcitationinhibitionmicrogliasynaptic plasticity

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Area of Science:

  • Neuroscience
  • Neuroinflammation
  • Synaptic Plasticity

Background:

  • Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine that influences neuronal synaptic plasticity.
  • The precise mechanisms by which TNFα mediates synaptic positive (change) and negative (stability) feedback remain unclear.

Purpose of the Study:

  • To investigate the effects of TNFα on microglia activation and synaptic transmission in mouse organotypic entorhino-hippocampal tissue cultures.
  • To elucidate the role of microglia in TNFα-induced synaptic plasticity and homeostasis.

Main Methods:

  • Organotypic entorhino-hippocampal slice cultures from mice were used.
  • Effects of varying concentrations of TNFα on excitatory and inhibitory neurotransmission were assessed.
  • Microglia activation and synaptic changes, including GluA1-containing AMPA receptor accumulation, were analyzed.
  • Experiments were conducted in both intact and microglia-depleted cultures.

Main Results:

  • TNFα modulated excitatory and inhibitory neurotransmission in a concentration-dependent manner.
  • Low TNFα concentrations strengthened glutamatergic transmission; higher concentrations increased inhibition.
  • Activated microglia induced homeostatic adjustment of excitatory synapses, returning strength to baseline within 24 hours while increasing inhibition.
  • In microglia-depleted cultures, TNFα-induced synaptic strengthening persisted.

Conclusions:

  • Microglia play a crucial role in TNFα-mediated synaptic plasticity and homeostasis.
  • Pro-inflammatory microglia act as negative feedback regulators, influencing neuronal plasticity and stability.
  • Microglia are essential gatekeepers of synaptic change and stability in the brain.