Md. Neely et Jg. Nicholls, ELECTRICAL-ACTIVITY, GROWTH CONE MOTILITY AND THE CYTOSKELETON, Journal of Experimental Biology, 198(7), 1995, pp. 1433-1446
The development of the nervous system takes place in two main steps: f
irst an extensive preliminary network is formed and then it is pruned
and trimmed to establish the final form, This refinement is achieved b
y mechanisms that include cell death, selective growth and loss of neu
rites and the stabilization and elimination of synapses, The focus of
this review is on selective neurite retraction during development, wit
h particular emphasis on the role of electrical activity, In many deve
loping vertebrate and invertebrate neurones, the frequency and duratio
n of ongoing impulse activity determine the final arborizations and th
e pattern of connections, When impulse traffic is silenced, axons fail
to retract branches that had grown to inappropriate destinations in t
he mammalian visual system, cerebellum and neuromuscular junctions, Si
milarly, in crustaceans, Drosophila melanogaster and leeches, refineme
nts in axonal morphology during development are influenced by impulse
activity, From experiments made in culture, it has been possible to mi
mic these events and to shaw a clear link between the density of volta
ge-activated calcium channels in a neurite and its retraction followin
g stimulation, The distribution of these calcium channels in turn is d
etermined by the substratum with which the neurites are in contact or
by the formation of synapses, Several lines of evidence suggest that c
alcium entry into the growth cone leads to collapse by disruption of a
ctin filaments, One candidate for coupling membrane events to neurite
retraction is the microfilament-associated protein gelsolin which, in
its calcium-activated state, severs actin filaments, Open questions th
at remain concern the differential effects of activity on dendrites an
d axons as well as the mechanisms by which the growth cone integrates
information derived from stimuli in the cell and in the extracellular
environment.