Input-specific spine entry of soma-derived Vesl-1S protein conforms to synaptic tagging

Late-phase synaptic plasticity depends on the synthesis of new proteins that must function only in the activated synapses. The synaptic tag hypothesis requires input-specific functioning of these proteins after undirected transport. Confirmation of this hypothesis requires specification of a biochemical tagging activity and an example protein that behaves as the hypothesis predicts. We found that in rat neurons, soma-derived Vesl-1S (Homer-1a) protein, a late-phase plasticity-related synaptic protein, prevailed in every dendrite and did not enter spines. N-methyl-d-aspartate receptor activation triggered input-specific spine entry of Vesl-1S proteins, which met many criteria for synaptic tagging. These results suggest that Vesl-1S supports the hypothesis and that the activity-dependent regulation of spine entry functions as a synaptic tag.