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Updated: Aug 17, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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.
Abstract:
The pro-inflammatory cytokine tumor necrosis factor α (TNFα) tunes the capacity of neurons to express synaptic plasticity. It remains, however, unclear how TNFα mediates synaptic positive (=change) and negative (=stability) feedback mechanisms. We assessed effects of TNFα on microglia activation and synaptic transmission onto CA1 pyramidal neurons of mouse organotypic entorhino-hippocampal tissue cultures. TNFα mediated changes in excitatory and inhibitory neurotransmission in a concentration-dependent manner, where low concentration strengthened glutamatergic neurotransmission via synaptic accumulation of GluA1-only-containing AMPA receptors and higher concentration increased inhibition. The latter induced the synaptic accumulation of GluA1-only-containing AMPA receptors as well. However, activated, pro-inflammatory microglia mediated a homeostatic adjustment of excitatory synapses, that is, an initial increase in excitatory synaptic strength at 3 h returned to baseline within 24 h, while inhibitory neurotransmission increased. In microglia-depleted tissue cultures, synaptic strengthening triggered by high levels of TNFα persisted and the impact of TNFα on inhibitory neurotransmission was still observed and dependent on its concentration. These findings underscore the essential role of microglia in TNFα-mediated synaptic plasticity. They suggest that pro-inflammatory microglia mediate synaptic homeostasis, that is, negative feedback mechanisms, which may affect the ability of neurons to express further plasticity, thereby emphasizing the importance of microglia as gatekeepers of synaptic change and stability.
Insights
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.
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.
