Tumor Necrosis Factor and Interleukin-1β Modulate Synaptic Plasticity during Neuroinflammation

Figure 2

Synaptic upscaling in response to physiological and pathological stimuli. (a) In a physiological state, during basal synaptic activity, AMPARs undergo constant cycles of membrane insertion and removal on postsynaptic neuron. When the synaptic strength driven by the presynaptic terminal is reduced, TNF, released by astroglia, activates a molecular mechanism leading to transient improved insertion of AMPARs on postsynaptic membrane. (b) During acute or chronic neuroinflammation, TNF, massively released by activated microglia and astroglia as well as infiltrating T-cells, indefinitely upregulates the mechanism of membrane AMPAR insertion. In parallel, inflammation affects physiological mechanisms of glutamate clearance at synaptic cleft. This together with enhanced glutamate release from glial cells over activates AMPARs, thus contributing to induce excitotoxic mechanisms and synaptic loss.

(a) Physiological condition

(b) Pathological condition