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

Abstract

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.

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Figure 1: Gross hippocampal anatomy is normal in Zif268−/− mice.
Figure 2: Short-term synaptic plasticity and LTP in the dentate gyrus of anesthetized Zif268 mutant mice.
Figure 3: LTP in the dentate gyrus of awake Zif268 mutant mice.
Figure 4: Expression of Zif268 in the dentate gyrus.
Figure 5: Spatial navigation in the water maze.
Figure 6: Conditioned taste aversion.
Figure 7: Discrimination learning at short and long delays.

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Acknowledgements

This work was supported in part by CNRS PICS programme (N°756). We thank P. Veyrac and M. Guegan for doing the immunohistochemistry, and S. Hiard for rearing and genotyping the mice.

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Correspondence to S. Davis.

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Jones, M., Errington, M., French, P. et al. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci 4, 289–296 (2001). https://doi.org/10.1038/85138

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