Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP

Neuron. 1999 Aug;23(4):787-98. doi: 10.1016/s0896-6273(01)80036-2.


It is hypothesized that Ca2+ stimulation of calmodulin (CaM)-activated adenylyl cyclases (AC1 or AC8) generates cAMP signals critical for late phase LTP (L-LTP) and long-term memory (LTM). However, mice lacking either AC1 or AC8 exhibit normal L-LTP and LTM. Here, we report that mice lacking both enzymes (DKO) do not exhibit L-LTP or LTM. To determine if these defects are due to a loss of cAMP increases in the hippocampus, DKO mice were unilaterally cannulated to deliver forskolin. Administration of forskolin to area CA1 before training restored normal LTM. We conclude that Ca2+-stimulated adenylyl cyclase activity is essential for L-LTP and LTM and that AC1 or AC8 can produce the necessary cAMP signal.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Avoidance Learning / physiology
  • Brain / drug effects
  • Brain / enzymology
  • Calcium / physiology*
  • Calmodulin / physiology
  • Colforsin / pharmacology
  • Cues
  • Electrophysiology
  • Fear / physiology
  • Fear / psychology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / physiology*
  • Immunohistochemistry
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal


  • Calmodulin
  • Colforsin
  • Adenylyl Cyclases
  • Calcium