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Glutamate regulates actin-based motility in axonal filopodia

Abstract

The dynamics of axonal arbors during synaptogenesis and their plasticity in the adult nervous system remain poorly understood. Axonal filopodia, which emerge from the shaft of axonal branches and contain small synaptic vesicle clusters, initiate synaptic formation. We found that the movement of axonal filopodia is strongly inhibited by the neurotransmitter glutamate. This inhibitory effect is local, requires extracellular Ca2+, and can be blocked by CNQX treatment but not by NMDA, implicating axonal AMPA/kainate glutamate receptors. Transport and exo-endocytic recycling of synaptic vesicle packages in filopodia are not affected. These results reveal that the effect of glutamate on axonal filopodia is similar to its previously described effect on dendritic spines. Our results raise the possibility that axonal ionotropic glutamate receptors are also involved in synaptic plasticity in the adult nervous system.

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Figure 1: Glutamate inhibits actin dynamics and filopodia motility in axons.
Figure 2: Actin-based motility of axonal filopodia before and after glutamate addition.
Figure 3: AMPA receptor activation arrests axonal filopodia motility.
Figure 4: The effect of glutamate on axonal filopodia is mediated by AMPA/kainate receptors and requires extracellular Ca2+.
Figure 5: Vesicle transport inside axons is not affected by glutamate treatment.
Figure 6: The inhibitory effect of glutamate on axons is local and does not spread to neighboring axonal filopodia.

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Acknowledgements

We thank K. Lee for assistance in preparing GFP-actin and L. Daniell for assistance in preparing the hippocampal cultures. S.C. is a Howard Hughes Medical Institute fellow of the Life Sciences Research Foundation. This work was supported in part by NIH grant to P.D.C. (NS36251).

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Correspondence to Pietro De Camilli.

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Chang, S., De Camilli, P. Glutamate regulates actin-based motility in axonal filopodia. Nat Neurosci 4, 787–793 (2001). https://doi.org/10.1038/90489

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