LOCALIZED SYNAPTIC ACTIONS OF NEUROTROPHIN-4

Neurotrophins secreted by the postsynaptic target cell may participate in activity-dependent synaptic modification during development and in the mature brain. A fundamental question of how neurotrophins can scu lpt synaptic connections is whether neurotrophin-induced synaptic chan ges are spatially restricted to the site of neurotrophin secretion or whether they can spread to neighboring synapses. Using a model system of nerve-muscle coculture in which neurotrophin-4, (NT-4) is overexpre ssed in a subpopulation of postsynaptic myocytes, we demonstrated that presynaptic potentiation is restricted to synapses on myocytes overex pressing NT-4 without affecting nearby synapses formed by the same neu ron on control myocytes. Likewise, postsynaptic modulation of acetylch oline channels by secreted NT-4 is spatially restricted to <60 mu m fr om the site of NT-4 secretion. Therefore, activity-dependent secretion of neurotrophins can result in highly localized modification of neuro nal connections.