Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses

Neuropharmacology. 2007 Jan;52(1):176-84. doi: 10.1016/j.neuropharm.2006.07.021. Epub 2006 Aug 8.


Long-term potentiation and depression (LTP and LTD) are cellular plasticity phenomena expressed at a variety of central synapses, and are thought to contribute to learning and developmental changes in circuitry. Recurrent neocortical layer-5 synapses are thought to express a presynaptic form of LTP that influences the short-term plasticity of the synapse. Here we show that changes in synaptic strength elicited by pairing high frequency pre- and postsynaptic firing at this synapse result from a mixture of presynaptic and postsynaptic forms of plasticity, as assessed by the analysis of changes in coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios. Pharmacological dissection of this plasticity revealed that block of presynaptic LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently presynaptic component of LTP could be prevented by induction in the presence of blockers of nitric oxide. These data suggest that correlated high-frequency firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD, presynaptic LTP, and postsynaptic LTP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cyclic N-Oxides / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Free Radical Scavengers / pharmacology
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neocortex / cytology*
  • Neuronal Plasticity / physiology*
  • Neurons / ultrastructure*
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / physiology*


  • Cyclic N-Oxides
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Imidazoles
  • Piperidines
  • Pyrazoles
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
  • AM 251
  • NG-Nitroarginine Methyl Ester