Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation.
It is an open question whether new synapses form during hippocampal LTP. Here, we show that late-phase LTP (L-LTP) is associated with a significant increase in numbers of synaptic puncta identified by synaptophysin and N-cadherin, an adhesion protein involved in synapse formation during development. During potentiation, protein levels of N-cadherin are significantly elevated and N-cadherin dimerization is enhanced. The increases in synaptic number and N-cadherin levels are dependent on cAMP-dependent protein kinase (PKA) and protein synthesis, both of which are also required for L-LTP. Blocking N-cadherin adhesion prevents the induction of L-LTP, but not the early-phase of LTP (E-LTP). Our data suggest that N-cadherin is synthesized during the induction of L-LTP and recruited to newly forming synapses. N-cadherin may play a critical role in L-LTP by holding nascent pre-and postsynaptic membranes in apposition, enabling incipient synapses to acquire function and contribute to potentiation.
Bozdagi
O
O
Fishberg Research Center for Neurobiology and the Program in Cell Adhesion, The Mount Sinai School of Medicine, New York, New York 10029, USA.
Shan
W
W
Tanaka
H
H
Benson
D L
DL
Huntley
G W
GW
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019281:Dimerization; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D019138:Antibodies, Blocking; D015820:Cadherins; D004791:Enzyme Inhibitors; D016708:Synaptophysin; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases