Abstract
BackgroundIn 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.Methodology/Principal FindingsWe 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/SignificanceTaken 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.
Highlights
It is generally believed that synapse-to-nucleus communication plays an important role for long-term memory formation [1,2,3]
Conclusions/Significance: Taken together, these findings suggest that the two major forms of NMDA-receptor dependent synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), elicit the transition of different synapto-nuclear messengers albeit in both cases importinmediated retrograde transport and NMDA-receptor activation is required
The induction of LTP leads to nuclear translocation of Jacob We first investigated whether Jacob translocates from dendritic compartments of the stratum radiatum to the nuclei of cornu ammonis 1 (CA1) neurons after tetanization of Schaffer-collateral inputs
Summary
It is generally believed that synapse-to-nucleus communication plays an important role for long-term memory formation [1,2,3]. Besides the transduction of synaptic Ca2+-signals via dendritic action potentials or intradendritic Ca2+-waves in recent years a growing number of synapto-nuclear protein messengers have been shown to enter the nucleus in response to NMDA-receptor (NMDAR) activation [3,4,5,6,7,8,9] These latter findings lead to the hypothesis that nucleocytoplasmic shuttling of proteins deriving from synapses and dendrites might be directly involved in plasticity-related gene expression and thereby contribute to memory formation [3,10]. We aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
