Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway

Neuron. 2004 Dec 16;44(6):997-1009. doi: 10.1016/j.neuron.2004.11.025.


The requirement for transcription during long-lasting plasticity indicates that signals generated at the synapse must be transported to the nucleus. We have investigated whether the classical active nuclear import pathway mediates intracellular retrograde signal transport in Aplysia sensory neurons and rodent hippocampal neurons. We found that importins localize to distal neuronal processes, including synaptic compartments, where they are well positioned to mediate synapse to nucleus signaling. In Aplysia, stimuli known to produce long-lasting but not short-lasting facilitation triggered importin nuclear translocation. In hippocampal neurons, NMDA receptor activation but not depolarization induced importin nuclear translocation. We further showed that LTP-inducing stimuli recruited active nuclear import in hippocampal slices. Together with our finding that long-term facilitation of Aplysia sensory-motor synapses required active nuclear import, our results indicate that regulation of the active nuclear import pathway plays a critical role in transporting synaptically generated signals into the nucleus during learning-related forms of plasticity.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Aplysia / metabolism
  • Aplysia / physiology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / physiology*
  • Cells, Cultured
  • Karyopherins / metabolism
  • Karyopherins / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Molecular Sequence Data
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • alpha Karyopherins / metabolism
  • alpha Karyopherins / physiology*


  • KPNA4 protein, human
  • Karyopherins
  • alpha Karyopherins
  • Serotonin

Associated data

  • GENBANK/AY536211