Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression

Neuron. 1998 Nov;21(5):1163-75. doi: 10.1016/s0896-6273(00)80633-9.


Hippocampal N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic depression (LTD) is associated with a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at a site (Ser-845) phosphorylated by cAMP-dependent protein kinase (PKA). In the present study, we show that dephosphorylation of a postsynaptic PKA substrate may be crucial for LTD expression. PKA activators inhibited both AMPA receptor dephosphorylation and LTD. Injection of a cAMP analog into postsynaptic neurons prevented LTD induction and reversed previously established homosynaptic LTD without affecting baseline synaptic transmission. Moreover, infusing a PKA inhibitor into postsynaptic cells produced synaptic depression that occluded homosynaptic LTD. These findings suggest that dephosphorylation of a PKA site on AMPA receptors may be one mechanism for NMDA receptor-dependent homosynaptic LTD expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Electric Stimulation
  • Enzyme Activation / drug effects
  • Hippocampus
  • In Vitro Techniques
  • Male
  • N-Methylaspartate / pharmacology
  • Phosphorylation / drug effects
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / metabolism
  • Synapses / enzymology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Thionucleotides / pharmacology


  • Receptors, AMPA
  • Thionucleotides
  • Colforsin
  • adenosine-3',5'-cyclic phosphorothioate
  • N-Methylaspartate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • glutamate receptor ionotropic, AMPA 1