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Long-Distance Integration of Nuclear ERK Signaling Triggered by Activation of a Few Dendritic Spines

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Science  29 Nov 2013:
Vol. 342, Issue 6162, pp. 1107-1111
DOI: 10.1126/science.1245622

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It Takes a Few

Persistent maintenance of long-term potentiation (LTP) of glutamatergic synapses and long-term memory requires neuronal nuclear signaling that leads to gene transcription. It is unclear whether signaling produced at a single dendritic spine can be transmitted into the nucleus to regulate gene transcription. Using two-photon glutamate uncaging in combination with two-photon fluorescence lifetime imaging, Zhai et al. (p. 1107) show that induction of LTP in only three to seven dendritic spines in a hippocampal pyramidal neuron can trigger activation of nuclear extracellular signal–regulated kinase and downstream transcription factors cyclic adenosine monophosphate response element–binding protein and E26-like transcription factor-1. Thus, signaling initiated in each dendritic spine can be transmitted into the nucleus to regulate gene transcription. Furthermore, biochemical signaling in multiple dendritic branches was integrated to activate the nuclear signaling.

Abstract

The late phase of long-term potentiation (LTP) at glutamatergic synapses, which is thought to underlie long-lasting memory, requires gene transcription in the nucleus. However, the mechanism by which signaling initiated at synapses is transmitted into the nucleus to induce transcription has remained elusive. Here, we found that induction of LTP in only three to seven dendritic spines in rat CA1 pyramidal neurons was sufficient to activate extracellular signal–regulated kinase (ERK) in the nucleus and regulate downstream transcription factors. Signaling from individual spines was integrated over a wide range of time (>30 minutes) and space (>80 micrometers). Spatially dispersed inputs over multiple branches activated nuclear ERK much more efficiently than clustered inputs over one branch. Thus, biochemical signals from individual dendritic spines exert profound effects on nuclear signaling.

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