Target-dependent release of a presynaptic neuropeptide regulates the formation and maturation of specific synapses in Aplysia

The correct wiring of neurons is critical for the normal functioning of the nervous system. Sensory neurons of Aplysia form synapses with specific postsynaptic targets. Interaction with appropriate target cells in culture induces a significant increase in axon growth, the number of sensory neuron varicosities with release sites contacting the target, and regulates the expression and distribution of mRNAs encoding presynaptic proteins such as syntaxin and the sensory neuron-specific neuropeptide sensorin. Synapse stabilization is accompanied by the maintenance of presynaptic varicosities and target-dependent regulation of mRNA distributions. We report here that specific targets induce the release of sensorin from sensory neurons, which then regulates synaptic efficacy, axonal growth associated with synapse formation, the maintenance of synaptic contacts, and the specific distribution of mRNAs. Bath application of an antisensorin antibody during the early phase of synapse formation blocked the expected increase in synaptic strength, the growth and formation of new presynaptic varicosities, and the target-dependent regulation of mRNA distribution. In contrast, bath application of sensorin accelerated the increase in synaptic strength and enhanced the formation of new varicosities and target-dependent regulation of mRNA distribution in sensory neurons. As synapses stabilize, sensorin secretion declines but is required for the maintenance of synaptic efficacy, presynaptic varicosities, and mRNA distributions. These results suggest that a retrograde target signal regulates the secretion and actions of a presynaptic neuropeptide critical for the formation and maintenance of specific synapses.