Prolonged activation of cAMP-dependent protein kinase during conditioning induces long-term memory in honeybees

Neuron. 2000 Jul;27(1):159-68. doi: 10.1016/s0896-6273(00)00017-9.


To investigate the function cAMP-dependent protein kinase (PKA) exerts in the induction of long-term memory, changes in PKA activity induced by associative learning in vivo were measured in the antennal lobes (ALs) of honeybees. The temporal dynamics of PKA activation depend on both the sequence of conditioned and unconditioned stimuli and the number of conditioning trials. Only multiple-trial conditioning, which induces long-term memory (LTM), leads to a profound prolongation of PKA activation mediated by the NO/cGMP system. Imitation of this prolonged PKA activation in the ALs in combination with single-trial conditioning is sufficient to induce LTM. These findings not only demonstrate the close connection between conditioning procedure and temporal dynamics in PKA activation but also reveal that already during conditioning a distinct temporal pattern of PKA activation is critical for LTM induction in intact animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Bees / physiology*
  • Brain / enzymology
  • Brain / physiology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cyclic GMP / physiology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Activators / pharmacology
  • Memory / drug effects
  • Memory / physiology*
  • Nitric Oxide / pharmacology
  • Photolysis
  • Sense Organs / drug effects
  • Sense Organs / physiology
  • Smell / drug effects
  • Smell / physiology
  • Thionucleotides / pharmacology


  • 8-bromoadenosine-3',5'-cyclic monophosphorothioate
  • Enzyme Activators
  • Thionucleotides
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Nitric Oxide
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP