Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein

Cell. 1994 Oct 7;79(1):59-68. doi: 10.1016/0092-8674(94)90400-6.


The cAMP-responsive element-binding protein (CREB) has been implicated in the activation of protein synthesis required for long-term facilitation, a cellular model of memory in Aplysia. Our studies with fear conditioning and with the water maze show that mice with a targeted disruption of the alpha and delta isoforms of CREB are profoundly deficient in long-term memory. In contrast, short-term memory, lasting between 30 and 60 min, is normal. Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation. However, paired-pulse facilitation and posttetanic potentiation are normal. These results implicate CREB-dependent transcription in mammalian long-term memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning
  • Conditioning, Psychological
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Electrophysiology
  • Female
  • Hippocampus / physiology
  • Long-Term Potentiation
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Neurologic Mutants
  • Mutation / physiology*


  • Cyclic AMP Response Element-Binding Protein