Neuronal pentraxins mediate synaptic refinement in the developing visual system

Lisa Bjartmar, Andrew D. Huberman, Erik M. Ullian, Rene C. Renteria, Xiaoquin Liu, Weifeng Xu, Jennifer Prezioso, Michael W. Susman, David Stellwagen, Caleb C. Stokes, Richard Cho, Paul Worley, Robert C. Malenka, Sherry Ball, Neal S. Peachey, David Copenhagen, Barbara Chapman, Masaru Nakamoto, Ben A. Barres, Mark S. Perin

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Abstract

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.

Original languageEnglish
Pages (from-to)6269-6281
Number of pages13
JournalJournal of Neuroscience
Volume26
Issue number23
DOIs
Publication statusPublished - Jun 2006

Keywords

  • retinogeniculate
  • neuronal pentraxins
  • synaptic plasticity
  • LTP
  • long-term potentiation
  • LTD
  • long-term depression
  • development
  • knock-out
  • retinal ganglion cell
  • lateral geniculate-nucleus
  • eye-specific segregation
  • calcium-binding protein
  • retinal ganglion-cells
  • nicotinic acetylcholine receptor
  • amyloid-P component
  • C-reactive protein
  • retinogeniculate projections
  • mammalian retina
  • BETA-2 subunit

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