| First Author | Heir R | Year | 2024 |
| Journal | J Neurosci | Volume | 44 |
| Issue | 14 | PubMed ID | 38395613 |
| Mgi Jnum | J:350701 | Mgi Id | MGI:7664317 |
| Doi | 10.1523/JNEUROSCI.2278-22.2024 | Citation | Heir R, et al. (2024) Astrocytes Are the Source of TNF Mediating Homeostatic Synaptic Plasticity. J Neurosci 44(14) |
| abstractText | Tumor necrosis factor alpha (TNF) mediates homeostatic synaptic plasticity (HSP) in response to chronic activity blockade, and prior work has established that it is released from glia. Here we demonstrate that astrocytes are the necessary source of TNF during HSP. Hippocampal cultures from rats of both sexes depleted of microglia still will increase TNF levels following activity deprivation and still express TTX-driven HSP. Slice cultures from mice of either sex with a conditional deletion of TNF from microglia also express HSP, but critically, slice cultures with a conditional deletion of TNF from astrocytes do not. In astrocytes, glutamate signaling is sufficient to reduce NFkappaB signaling and TNF mRNA levels. Further, chronic TTX treatment increases TNF in an NFkappaB-dependent manner, although NFkappaB signaling is dispensable for the neuronal response to TTX-driven HSP. Thus, astrocytes can sense neuronal activity through glutamate spillover and increase TNF production when activity falls, to drive HSP through the production of TNF. |
