The long-term objective of the work is to contribute to an understanding of subcellular and molecular events underlying synapse formation during development, regeneration and long-term synaptic plasticity.
The specific aim here is to assess the importance of the regulation of actin-based motility in synapse formation. It is hypothesized that, during development and regeneration, suppression of actin-based motility is a key early step in the interaction of the tip of a growing axon with the site at which it will form a synapse. This hypothesis will be tested using models of two different types of synapse formation. One is of the type in which the ingrowing axon stops at a site and forms a single synapse. Here, high resolution VEC-DIC microscopy will be used to determine the mechanism whereby a peptide concentrated at the neuromuscular junction, LRE, specifically acts on the growth cone of the motor neuron to stop axon growth. The other model is of the type in which multiple, spatially discrete en passant synapses are formed by the axon growing along its target. Here, video-intensified fluorescence microscopy will be used to observe the interaction in culture of growth cones of an identified Aplysia sensory neuron with specific target sites on its motor neuron partner. Long-term increases in adult synaptic efficacy may be caused by the formation of new synapses. In at least some cases this is associated with the growth of axonal arbor. It is hypothesized that induction of actin-based motility is the first step in this growth. This hypothesis will be tested using video-intensified fluorescence microscopy with the Aplysia sensory neuron/motor neuron coculture, which displays such plasticity. An identification of specific changes in motility should point to specific molecular targets within the presynaptic element for signals regulating synapse formation during development, regeneration and synaptic plasticity.
|Hatada, Y; Wu, F; Sun, Z Y et al. (2000) Presynaptic morphological changes associated with long-term synaptic facilitation are triggered by actin polymerization at preexisting varicositis. J Neurosci 20:RC82|
|Hatada, Y; Wu, F; Silverman, R et al. (1999) En passant synaptic varicosities form directly from growth cones by transient cessation of growth cone advance but not of actin-based motility. J Neurobiol 41:242-51|