Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 30, Pages 8031-8039Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2003-07.2007
Keywords
cofilin; actin; PSD-95; phosphorylation; unsupervised learning; immunoreactivity
Categories
Funding
- NIA NIH HHS [5T32-AG00358] Funding Source: Medline
- NINDS NIH HHS [R01 NS051823, NS051823, NS045260, P01 NS045260] Funding Source: Medline
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Stabilization of long-term potentiation (LTP) depends on multiple signaling cascades linked to actin polymerization. We used one of these, involving phosphorylation of the regulatory protein cofilin, as a marker to test whether LTP-related changes occur in hippocampal synapses during unsupervised learning. Well handled rats were allowed to explore a compartmentalized environment for 30 min after an injection of vehicle or the NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Another group of rats consisted of vehicle-injected, home-cage controls. Vehicle-treated rats that explored the environment had 30% more spines with dense phosphorylated (p) cofilin immunoreactivity in hippocampal field CA1 than did rats in the home-cage group. The increase in pCofilin-positive spines and behavioral evidence for memory of the explored environment were both eliminated by CPP. Coimmunostaining for pCofilin and the postsynaptic density protein 95 (PSD-95) showed that synapses on pCofilin-positive spines were substantially larger than those on neighboring (pCofilin-negative) spines. These results establish that uncommon cellular events associated with LTP, including changes in synapse size, occur in individual spines during learning, and provide a technique for mapping potential engrams.
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