title: Evidence that long-term potentiation occurs within individual hippocampal synapses during learning.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92617-4291, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Fedulov
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Rex
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Simmons
authors.forename: Linda
authors.initials: L
authors.lastname: Palmer
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gall
authors.forename: Gary
authors.initials: G
authors.lastname: Lynch
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D010879:Piperazines; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid