Activity-dependent gene transcription is known to be of vital importance for long-lasting neural plasticity. Major efforts have therefore been undertaken in recent years to elucidate how biochemical signals initiated at the synapse are conveyed to the nucleus. But why is signaling from the synapse to the nucleus and back a significant cell biological problem? Synaptic plasticity defined broadly as any form of use-dependent change in synapto-dendritic input covering a broad range of plasticity phenomena, including LTP and LTD, is known to be established at individual synapses. Intuitively, one might therefore assume that a privileged connection exists between synapses undergoing plastic events and activity-dependent

*AG 'Molecular Mechanisms of Plasticity', Department of Neurochemistry/Mol. Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany; [email protected]

nuclear gene transcription that will eventually stabilize synaptic changes for long periods. Signaling from the individual synapse to the nucleus has been convincingly shown to exist in invertebrate model systems1'2. It has, however, been particularly hard to establish such signaling pathways in vertebrate neurons. One major problem has been to demonstrate that the translocation of molecules to the nucleus is initiated at a single synapse. Alternatively, it could result from the net activity of many synapses that is integrated in the somatic cytoplasm from where then transcriptional regulators will eventually enter the nucleus. Moreover, it is largely unclear why and more precisely which type of gene transcription is actually necessary for long-term plasticity processes. Finally, it remains to be resolved how altered gene expression feeds back to the activated synapses that originally induced it.

To address these questions we initially review the present knowledge how synaptic activity might regulate the major signaling pathways that have been shown to trigger nuclear gene transcription in response to synaptic activation in vertebrate neurons. We then summarize how these pathways are integrated at the level of the nucleus. Another part of the chapter is devoted to the question how plasticity-driven gene transcription might feed back to the synapse. The scope of the chapter is limited to signaling pathways from the excitatory postsynaptic compartment to the nucleus, excluding signaling pathways from the inhibitory synapse or retrograde presynaptic signaling, since less is known about such pathways.

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