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CPG15 regulates synapse stability in the developing and adult brain.

Use-dependent selection of optimal connections is a key feature of neural circuit development and, in the mature brain, underlies functional adaptation, such as is required for learning and memory. Activity patterns guide circuit refinement through selective stabilization or elimination of specific neuronal branches and synapses. The molecular signals that mediate activity-dependent synapse and arbor stabilization and maintenance remain elusive. We report that knockout of the activity-regulated gene cpg15 in mice delays developmental maturation of axonal and dendritic arbors visualized by anterograde tracing and diolistic labeling, respectively. Electrophysiology shows that synaptic maturation is also delayed, and electron microscopy confirms that many dendritic spines initially lack functional synaptic contacts. While circuits eventually develop, in vivo imaging reveals that spine maintenance is compromised in the adult, leading to a gradual attrition in spine numbers. Loss of cpg15 also results in poor learning. cpg15 knockout mice require more trails to learn, but once they learn, memories are retained. Our findings suggest that CPG15 acts to stabilize active synapses on dendritic spines, resulting in selective spine and arbor stabilization and synaptic maturation, and that synapse stabilization mediated by CPG15 is critical for efficient learning.

Pubmed ID: 22190461

Authors

  • Fujino T
  • Leslie JH
  • Eavri R
  • Chen JL
  • Lin WC
  • Flanders GH
  • Borok E
  • Horvath TL
  • Nedivi E

Journal

Genes & development

Publication Data

December 15, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK080000
  • Agency: NIDDK NIH HHS, Id: DP1 DK098058
  • Agency: NIH HHS, Id: DP1 OD006850
  • Agency: NEI NIH HHS, Id: R01 EY011894
  • Agency: NEI NIH HHS, Id: R01 EY011894

Mesh Terms

  • Animals
  • Axons
  • Brain
  • Dendritic Spines
  • GPI-Linked Proteins
  • Learning
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neurons
  • Synapses