Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory

Neuron. 2002 Apr 25;34(3):447-62. doi: 10.1016/s0896-6273(02)00684-0.


CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal hippocampus, but not context conditioning, which does not. The deficit is specific to long-term memory, as shown in an object recognition task. Several forms of late-phase LTP are normal, but forskolin-induced and dopamine-regulated potentiation are disrupted. These experiments represent the first targeting of the dorsal hippocampus in genetically modified mice and confirm a role for CREB in hippocampus-dependent learning. Nevertheless, they suggest that some experimental forms of plasticity bypass the requirement for CREB.

Publication types

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

MeSH terms

  • Activating Transcription Factor 1
  • Animals
  • Behavior / physiology
  • Brain / anatomy & histology
  • Brain / physiology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Enkephalins / genetics
  • Enkephalins / metabolism
  • Female
  • Hippocampus / anatomy & histology
  • Hippocampus / physiology*
  • Humans
  • In Situ Hybridization
  • Long-Term Potentiation / physiology
  • Male
  • Maze Learning
  • Memory / physiology*
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / physiology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transgenes


  • Activating Transcription Factor 1
  • Atf1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Enkephalins
  • Protein Precursors
  • Transcription Factors
  • proenkephalin