In this study, we therefore fill an important gap regarding the proposed functional role of synapto-nuclear protein messengers in cellular plasticity. We can show that at least one member of this growing group exhibits highly dynamic trafficking from dendrites to the nucleus already during the WY 14643 tetanization period of LTP in hippocampal slices in vitro. Importantly, nuclear trafficking of Jacob is already detected during the induction of LTP. Frey and co-workers have shown that the requirement for transcription in order to maintain LTP may have a critical time window, because the blocker of gene transcription actinomycin D was only effective in influencing the maintenance of LTP when applied before tetanization, while it was ineffective when it was administered shortly after tetanization. Accordingly, one might argue that trafficking of synaptonuclear protein messengers might be to slow to enter the nucleus to be involved in plasticity-related gene expression in this cellular model of learning and memory. Our results strongly suggest that this is not the case. We could show that Jacob deriving from dendrites is capable of entering the nucleus within a few minutes during tetanization of the slices. Interestingly, during the course of these experiments, we realized that already the preparation of slices led to higher levels of Jacob in the nucleus than seen in sections stained with the same Jacob antibody from perfused animals. Thus, the increase in nuclear Jacob might be even larger in models of in vivo LTP or LTD where no uncontrolled release of glutamate due to neuronal injury during preparation of the slices will drive Jacob into the nucleus. It should also be noted that Jacob immunostainings suggest a prominent association of the protein with the nuclear ASP1517 side effects membrane. It will be interesting to analyze whether the protein is mainly associated with the inner or the outer nuclear membrane. Taken together, these findings suggest that Jacob might be involved in the control of gene expression to maintain LTP type of synaptic plasticity. It will be interesting to investigate whether other putative synapto-nuclear messenger than CREB2 or Jacob exhibit similar specificity concerning activity-dependent nuclear import following induction of synaptic plasticity. Since trafficking from distal dendrites supposedly requires association with specific importins, the question arises at which levels these different forms of plasticity regulate these processes. One possibility could be that different importins are involved in synapse-to-nucleus trafficking during induction of LTD and LTP. All members of the importin-a and -b family are expressed in brain at different levels and previous work has shown that induction of chemical LTP in hippocampal slices leads to increased nuclear import of importina1, a2 and b1.