Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons

Abstract

The authors report that the immediate-early gene Narp accumulates at excitatory synapses on parvalbumin-expressing interneurons. Narp recruits AMPA receptors at excitatory synapses to rebalance network excitation and inhibition dynamics. 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 Narp (neuronal activity–regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp−/− mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp−/− mice had 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.