Microglia modulate TNF[alpha]‐mediated synaptic plasticity

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Glia. - 71, 9 (2023) , 2117-2136, ISSN: 1098-1136

Klassifikation
Medizin, Gesundheit

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2023

DOI
10.1002/glia.24383
URN
urn:nbn:de:bsz:25-freidok-2365918
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:50 MEZ

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  • 2023

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