Long-term memory formation requires anterograde transport of proteins from the soma of a neuron to its distal synaptic terminals. This allows new synaptic connections to be grown and existing ones remodeled. However, we do not yet know which proteins are transported to synapses in response to activity and temporal regulation. Here, using quantitative mass spectrometry, we have profiled anterograde protein cargos of a learning-regulated molecular motor protein kinesin (ApKHC1) following short-term sensitization (STS) and long-term sensitization (LTS) inAplysia californica. Our results reveal enrichment of specific proteins associated with ApKHC1 following both STS and LTS, as well as temporal changes within one and three hours of LTS training. A significant number of proteins enriched in the ApKHC1 complex participate in synaptic function, and while some are ubiquitously enriched across training conditions, a few are enriched in response to specific training. For instance, factors aiding new synapse formation, such as synaptotagmin-1, dynamin-1, and calmodulin, are differentially enriched in anterograde complexes one hour after LTS but are depleted three hours after LTS. Proteins including gelsolin-like protein 2 and sec23A/sec24A, which function in actin filament stabilization and vesicle transport, respectively, are enriched in cargos three hours after LTS. These results establish that the composition of anterograde transport complexes undergo experience dependent specific changes and illuminate dynamic changes in the communication between soma and synapse during learning.Significance StatementDespite advances in our understanding of mechanisms underlying activity-dependent transport from soma to synapse, the specific gene products transported to synapses during learning are not yet understood in any system. Employing quantitative proteomic analysis of an anterogradely transported protein complex, we find that this complex undergoes dynamic compositional changes during short-term and long-term sensitization training. These findings bring new insights into the regulation of soma-to-synapse communication during learning.

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