The critical role of axonal transport in supplying macromolecules required to maintain the structure and physiological activity of the neuron is well-documented. By contrast, relatively little attention has been focused on whether physiological activity, in turn, modulates axonal transport. We have obtained preliminary evidence from in vitro studies that electrical stimulation of the sciatic nerve or the dorsal root ganglion (DRG) inhibits the amount of newly-synthesized protein delivered to the fast transport system in the axon. The effect is frequency-dependent and occurs under conditions where protein synthesis is unaffected. Further experiments are required to strengthen the potential physiological relevance of this coupling between excitation and intracellular transport. We propose to characterize the phenomenon by examining whether it is mediated by Ca2+, whether transport reverts to normal or to higher levels following stimulation and whether all fast- transported proteins are affected to a similar extent. The effects of impulse activity on the amount of fast-transported radiolabeled protein will be examined in sympathetic ganglia as well as dorsal root ganglia of the bullfrog. This will test not only the generalization of the phenomenon but will allow comparison of the effects of non-synaptic and synaptic stimulation. Morphological correlates of the effect will be examined first by checking for impulse-dependent alterations of somal ultrastructure. We will also utilize video-enhanced light microscopy to determine how the stimulation-induced decrease in amount of radiolabeled protein is reflected in the anterograde transport of newly-formed organelles. These collective studies may also enable us to begin to identify the subcellular site(s) at which impulse activity perturbs the delivery of newly-synthesized materials to the axon.
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| Tang, H Z; Hammerschlag, R; Chan, H et al. (1995) Changes in fast axonal transport in sensory neurons during tadpole metamorphosis. Int J Dev Neurosci 13:473-81 |
| Smith, R S; Hammerschlag, R; Snyder, R E et al. (1994) Action of brefeldin A on amphibian neurons: passage of newly synthesized proteins through the Golgi complex is not required for continued fast organelle transport in axons. J Neurochem 62:1698-706 |
| Hammerschlag, R (1994) Is the intrasomal phase of fast axonal transport driven by oscillations of intracellular calcium? Neurochem Res 19:1431-7 |
