Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation

Neuron. 2000 Oct;28(1):245-59. doi: 10.1016/s0896-6273(00)00100-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Cadherins / metabolism*
  • Cyclic AMP / analogs & derivatives*
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dimerization
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*
  • Synaptophysin / metabolism
  • Thionucleotides / pharmacology

Substances

  • Antibodies, Blocking
  • Cadherins
  • Enzyme Inhibitors
  • Synaptophysin
  • Thionucleotides
  • adenosine-3',5'-cyclic phosphorothioate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases