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Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology

Abstract

Memory storage in mammalian neurons probably depends on both biochemical events and morphological alterations in dendrites. Here we report an activity-dependent stabilization of the MAP kinase (MAPK) pathway, prominent in hippocampal dendrites. The longevity of the signal in these dendrites was increased to hours when multiple spaced stimuli were used. Likewise, spaced stimuli and MAPK activation were critical for protrusion of new dendritic filopodia that also remained stable for hours. Our experiments define a new role for stimulus-specific responses of MAPK signaling in activity-dependent neuronal plasticity. The local biochemical signaling in dendrites complements MAPK signaling in gene expression. Together, these processes may support long-lasting behavioral changes.

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Figure 1: The duration of activation of MAPK in hippocampal neurons is critically dependent on the pattern of membrane depolarization.
Figure 2: PKA gates a persistent MEK activation to stabilize dendritic MAPK phosphorylation.
Figure 3: Contrasting effects of dominant negative forms of Ras and Rap1.
Figure 4: Continuous upstream activation of MEK during the post-stimulus stabilized state.
Figure 5: Activity-dependent structural plasticity in hippocampal neurons depends on MAPK signaling.
Figure 6: Dynamics of structural plasticity.
Figure 7: Stability of structural plasticity.

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Acknowledgements

We thank H. Cline and H. Reuter for reading the manuscript, and members of the Tsien lab for comments and discussion. We also thank Y.-Q. Cao for her help in the western blot experiments. This study was supported by the NIH.

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Correspondence to Richard W. Tsien.

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Wu, GY., Deisseroth, K. & Tsien, R. Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat Neurosci 4, 151–158 (2001). https://doi.org/10.1038/83976

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