Effects Of Tetrodotoxin On Dendrite Growth

Important evidence for involvement of neuronal activity in dendrite growth comes from pharmacological blockade of activity. Exposing developing neurons to tetrodotoxin (TTX), which blocks action potential-mediated transmission, has yielded varying effects on dendrite growth. In acute cortical slices, TTX exposure increases density and length of interstitial shaft filopodia, without affecting their motility, half-life or turnover, and filopodia associated with growth cones are insensitive to TTX13. TTX did not prevent afferent innervation-induced dendrite growth in hippocampal co-cultures43. Exposure to TTX in the eye or LGN in mammals produced no detectable effects on arborization of LGN dendrites49,50. Dendritic growth of axolotl Mauthner cells has been shown to be driven by afferent innervation that is TTX insensitive51. TTX also failed to alter dendrite growth in vivo in Xenopus laevis optic tectum17 or filopodial motility of developing RGCs in retinal explants26. However, in ferret cortical brain slices, TTX blocks neurotrophin-induced dendritic growth52. The action of TTX to eliminate action potential-mediated synaptic transmission, but leaving spontaneous vesicular neurotransmitter release, induces a switch from strong correlated input to spontaneous weak innervation. Thus activity-driven events normally regulated by relative amounts of innervation from each synaptic contact would be removed, but activity-dependent mechanisms that can be driven by weak spontaneous input, as well as activity-independent mechanisms remain.

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