title: Nuclear translocation of jacob in hippocampal neurons after stimuli inducing long-term potentiation but not long-term depression.
abstract: BACKGROUND
  In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity.
  
  
  RESULTS
  We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels.
  
  
  CONCLUSIONS
  Taken together, these findings suggest that the two major forms of NMDA-receptor dependent synaptic plasticity, LTP and LTD, elicit the transition of different synapto-nuclear messengers albeit in both cases importin-mediated retrograde transport and NMDA-receptor activation is required.
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai, China. behnish@fudan.edu.cn
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnisch
authors.forename: Pingan
authors.initials: P
authors.lastname: Yuanxiang
authors.forename: Philipp
authors.initials: P
authors.lastname: Bethge
authors.forename: Suhel
authors.initials: S
authors.lastname: Parvez
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.forename: Anna
authors.initials: A
authors.lastname: Karpova
authors.forename: Julietta U
authors.initials: JU
authors.lastname: Frey
authors.forename: Marina
authors.initials: M
authors.lastname: Mikhaylova
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; C504443:Nsmf protein, rat; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins