Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing 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 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.
Chang
Michael C
MC
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Park
Joo Min
JM
Pelkey
Kenneth A
KA
Grabenstatter
Heidi L
HL
Xu
Desheng
D
Linden
David J
DJ
Sutula
Thomas P
TP
McBain
Chris J
CJ
Worley
Paul F
PF
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005110:Extracellular Space / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D007696:Kindling, Neurologic / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D000099153:Pentraxins
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D018091:Receptors, AMPA; D000099153:Pentraxins; C104724:glutamate receptor ionotropic, AMPA 4