A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories

Nat Neurosci. 2001 Mar;4(3):289-96. doi: 10.1038/85138.


The induction of long-term potentiation (LTP) in the dentate gyrus of the hippocampus is associated with a rapid and robust transcription of the immediate early gene Zif268. We used a mutant mouse with a targeted disruption of Zif268 to ask whether this gene, which encodes a zinc finger transcription factor, is required for the maintenance of late LTP and for the expression of long-term memory. We show that whereas mutant mice exhibit early LTP in the dentate gyrus, late LTP is absent when measured 24 and 48 hours after tetanus in the freely moving animal. In both spatial and non-spatial learning tasks, short-term memory remained intact, whereas performance was impaired in tests requiring long-term memory. Thus, Zif268 is essential for the transition from short- to long-term synaptic plasticity and for the expression of long-term memories.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics / pharmacology
  • Animals
  • Avoidance Learning / physiology
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Discrimination Learning / physiology
  • Early Growth Response Protein 1
  • Excitatory Postsynaptic Potentials / physiology
  • Genes, Immediate-Early / physiology*
  • Immediate-Early Proteins*
  • Long-Term Potentiation / genetics*
  • Maze Learning / physiology
  • Memory / physiology*
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Memory, Short-Term / physiology
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / genetics*
  • Neurons / cytology
  • Neurons / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics*


  • Anesthetics
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Immediate-Early Proteins
  • RNA, Messenger
  • Transcription Factors