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The Journal of Neuroscience, July 25, 2007, 27(30):8031-8039; doi:10.1523/JNEUROSCI.2003-07.2007
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Behavioral/Systems/Cognitive
Evidence That Long-Term Potentiation Occurs within Individual Hippocampal Synapses during Learning
Vadim Fedulov,1
Christopher S. Rex,2
Danielle A. Simmons,3
Linda Palmer,4
Christine M. Gall,1,2 and
Gary Lynch3
Departments of 1Anatomy and Neurobiology, 2Neurobiology and Behavior, and 3Psychiatry and Human Behavior, University of California, Irvine, California 92617-4291, and 4Department of Philosophy, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213
Correspondence should be addressed to Gary Lynch, 101 Theory Drive, #250, University of California, Irvine, CA 92612-1695. Email: glynch{at}uci.edu
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.
Key words: cofilin; actin; PSD-95; phosphorylation; unsupervised learning; immunoreactivity
Received May 2, 2007;
revised June 14, 2007;
accepted June 14, 2007.
Correspondence should be addressed to Gary Lynch, 101 Theory Drive, #250, University of California, Irvine, CA 92612-1695. Email: glynch{at}uci.edu
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