Molecular mechanisms underlying a cellular analog of operant reward learning

Neuron. 2008 Sep 11;59(5):815-28. doi: 10.1016/j.neuron.2008.07.019.


Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analog of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor, and by expressing a dominant-negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aplysia
  • Behavior, Animal
  • Calcium / metabolism
  • Cells, Cultured
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Dopamine / pharmacology
  • Electric Stimulation / methods
  • Ganglia, Invertebrate / cytology
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / radiation effects
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Patch-Clamp Techniques
  • Peptide Fragments / pharmacology
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Transport / drug effects
  • Reward*
  • Serine / metabolism
  • Thionucleotides / pharmacology


  • Intracellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Protein Kinase Inhibitors
  • Thionucleotides
  • protein kinase inhibitor peptide (6-24)
  • adenosine-3',5'-cyclic phosphorothioate
  • Serine
  • Cyclic AMP
  • Protein Kinase C
  • Calcium
  • Dopamine