Novel protein kinase A-dependent long-term depression of excitatory synapses

Neuron. 2002 Dec 5;36(5):921-31. doi: 10.1016/s0896-6273(02)01051-6.


Dopamine neurons of the ventral tegmental area (VTA) are critically involved in processing novel and rewarding information, and mediate the addictive properties of many drugs of abuse. Excitatory synapses on these neurons, like those in other brain regions, exhibit long-term depression (LTD). Amphetamine or dopamine block LTD at VTA synapses, indicating that both pathological and local physiological stimuli regulate LTD. Here we show that in common with other forms of LTD, VTA LTD results from a selective decrease in AMPA receptor function accompanied by a decrease in cell surface AMPA receptors. However, unlike the case for any previously described form of LTD, activation of cyclic AMP-dependent protein kinase (PKA) is necessary and sufficient to trigger LTD at synapses on VTA dopamine neurons.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dopamine / metabolism
  • Enzyme Activation
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Long-Term Synaptic Depression / physiology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / physiology
  • Synapses / physiology*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism


  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium
  • Dopamine