Signaling Between Synapse and Nucleus During Synaptic Plasticity

The requirement for transcription during synapse formation and longlasting synaptic plasticity raises two cell biological questions regarding communication between the synapse and nucleus in neurons. First, how are signals transmitted from stimulated synapses to the nucleus to initiate changes in gene expression? Second, how do the products of gene expression function to alter the structure and function of some but not all synapses made by a given neuron? We address these questions in two model systems of synapse formation and synaptic plasticity: cultured sensory-motor neurons from the marine mollusk, Aplysia californica, and cultured rodent hippocampal neurons. In studying signaling from synapse to nucleus, we have discovered a role for the importin family of nuclear transporters in carrying signals from synapses to the nucleus during long-term plasticity. Importins are present at synapses, travel to the nucleus following stimuli that elicit transcription, and are required for the long-term plasticity of Aplysia sensory-motor synapses. In studying how the products of transcription are targeted to specific synapses within a neuron, we have focused on the role of mRNA localization and regulated translation at the synapse. We have identified hundreds of mRNAs that are present in distal processes of Aplysia neurons and in dendrites of rodent hippocampal neurons. We find that localized mRNAs are translated at sites of synaptic contact during synapse formation and following stimulation that elicits long-lasting synaptic plasticity. It will be of interest to determine how these long-range, synapse-to-nucleus signal transduction pathways are altered with aging and during neurodegeneration.