Neuroimmune regulation of homeostatic synaptic plasticity

•TNFα, class I MHC and Narp are directly involved in homeostatic synaptic plasticity.•Class I MHC, NP1, Narp and Cbln1 can homeostatically regulate synapse formation.•TNFα and class I MHC regulate homeostatic plasticity of visual cortex in vivo.•Neuroimmune molecules may link homeostatic and Hebbian plasticity mechanisms.

Homeostatic synaptic plasticity refers to a set of negative-feedback mechanisms that are used by neurons to maintain activity within a functional range. While it is becoming increasingly clear that homeostatic regulation of synapse function is a key principle in the nervous system, the molecular details of this regulation are only beginning to be uncovered. Recent evidence implicates molecules classically associated with the peripheral immune system in the modulation of homeostatic synaptic plasticity. In particular, the pro-inflammatory cytokine TNFα, class I major histocompatibility complex, and neuronal pentraxin 2 are essential in the regulation of the compensatory synaptic response that occurs in response to prolonged neuronal inactivity. This review will present and discuss current evidence implicating neuroimmune molecules in the homeostatic regulation of synapse function.This article is part of the Special Issue entitled ‘Homeostatic Synaptic Plasticity’.