Neuronal pentraxins mediate synaptic refinement in the developing visual system.
Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.
Bjartmar
Lisa
L
Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Huberman
Andrew D
AD
Ullian
Erik M
EM
Rentería
René C
RC
Liu
Xiaoqin
X
Xu
Weifeng
W
Prezioso
Jennifer
J
Susman
Michael W
MW
Stellwagen
David
D
Stokes
Caleb C
CC
Cho
Richard
R
Worley
Paul
P
Malenka
Robert C
RC
Ball
Sherry
S
Peachey
Neal S
NS
Copenhagen
David
D
Chapman
Barbara
B
Nakamoto
Masaru
M
Barres
Ben A
BA
Perin
Mark S
MS
D000818:Animals; D002097:C-Reactive Protein / Q000502:physiology*; D002478:Cells, Cultured; D005829:Geniculate Bodies / Q000254:growth & development / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development / Q000502:physiology*; D000099153:Pentraxins
D002097:C-Reactive Protein; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D000099153:Pentraxins