Control of Synaptic Strength by Glial TNFα

TLDR

Activity‑dependent modulation of synaptic efficacy drives neural circuit development and experience‑dependent plasticity, yet the influence of glia on synaptic strength has largely been ignored. The study examines whether glial tumor necrosis factor α (TNFα) modulates synaptic efficacy. TNFα enhances synaptic efficacy by increasing surface expression of AMPA receptors. Blocking endogenous TNFα reduces synaptic strength, showing that continuous TNFα presence is required to preserve excitatory synaptic strength, likely through AMPA receptor trafficking.

Abstract

Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor α (TNFα), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFα has the opposite effects. Thus, the continual presence of TNFα is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFα may play roles in synaptic plasticity and modulating responses to neural injury.