Narp regulates homeostatic scaling of excitatory synapses on Parvalbumin interneurons

Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity, and involves both excitatory and inhibitory neurons. The immediate-early gene termed Narp (Neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind and cluster AMPA receptors (AMPARs). Here, we report that Narp prominently accumulates at excitatory synapses on Parvalbumin-expressing interneurons (PV-INs). Increasing network activity results in a homeostatic increase of excitatory synaptic strength onto PV-INs that increases inhibitory drive, and this response is absent in neurons cultured from Narp knock-out (Narp(−/−)) mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices are also dependent on Narp, and Narp(−/−) mice display increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.