TNF-dependent regulation of synaptic plasticity and neuronal activity: implications for psychiatric disorders.

Abstract

Over 20 years ago, it was established that the pro-inflammatory cytokine tumor necrosis factor-α (TNF) can directly regulate neurotransmitter receptor trafficking. On pyramidal neurons, TNF signaling results in the synaptic insertion of AMPA receptors and the removal of GABA_A receptors, shifting the excitatory/inhibitory balance to a more excitable state. The glial release of TNF mediates homeostatic synaptic plasticity (HSP), a compensatory form of plasticity in response to chronic decreases in neuronal activity. This adaptive response can stabilize neuronal circuits, which may be beneficial during development and in certain psychiatric conditions. However, the homeostatic set-point may be dynamically regulated, in a process akin to allostasis. Under these conditions, TNF may act to create or maintain the altered circuit function underlying psychiatric disorders and disease states.