CPG15 regulates synapse stability in the developing and adult brain
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Nedivi_CPG15 regulates.pdf
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Author(s)
Fujino, Tadahiro
Leslie, Jennifer H.
Eavri, Ronen
Chen, Jerry L.
Borok, Erzsebet
Horvath, Tamas L.
Nedivi, Elly
Lin, Walter C
Flanders, Genevieve
Date Issued
December 2011
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Fujino, T., J. H. Leslie, R. Eavri, J. L. Chen, W. C. Lin, G. H. Flanders, E. Borok, T. L. Horvath, and E. Nedivi. “CPG15 Regulates Synapse Stability in the Developing and Adult Brain.” Genes & Development 25, no. 24 (December 15, 2011): 2674–2685. © 2011 by Cold Spring Harbor Laboratory Press
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Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Article is available under a Creative Commons license; see publisher’s site for details.
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DOI of Published Version
https://doi.org/10.1101/gad.176172.111
