M. Nachmanclewner et E. Townesanderson, INJURY-INDUCED REMODELING AND REGENERATION OF THE RIBBON PRESYNAPTIC TERMINAL IN-VITRO, Journal of neurocytology, 25(10), 1996, pp. 597-613
The neuronal response to axonal injury may relate to the type of insul
t incurred. Recently, neuritic and presynaptic varicosity regeneration
by isolated adult salamander photoreceptors was demonstrated. We have
used this system to compare the rod photoreceptor response to two typ
es of injury: denervation/detargeting, the removal of pre- and postsyn
aptic partners from the axon terminal, and axotomy, the removal of the
axon terminal itself. Cells were followed with time-lapse video micro
scopy for 24-48 h in culture and immunolabelled for SV2 or synaptophys
in to identify synaptic vesicle-containing varicosities. Although all
injured cells responded with regenerative growth, denervated/detargete
d photoreceptors (i.e. neurons which retain their axon terminal) grew
80% more processes and fourfold more presynaptic varicosities than axo
tomized neurons. In cells which retained their original axon and termi
nal, varicosity formation generally began with axon retraction. Retrac
tion was followed by elaboration of a lamellipodium and, by 48 h, deve
lopment of varicosity-bearing neurites from the lamellipodium. Synapti
c vesicle protein localization in denervated/detargeted cells parallel
ed axon terminal reorganization. Axotomized cells, in contrast, lacked
synaptic vesicle protein immunoreactivity during this period. To dete
ct synaptic protein synthesis, photoreceptors were examined for coloca
lization of synaptic vesicle protein with rab6, a Golgi marker, by con
focal microscopy. As expected, synaptic vesicle protein staining was p
resent in the Golgi complex during regeneration; however, in cells wit
h an axon, new synaptic vesicle protein-labelled varicosities were fou
nd at early stages, prior to the appearance of immunolabel in the Golg
i complex. The data demonstrate remarkable plasticity in the ribbon sy
napse, and suggest that in adult rod cells with an intact axon termina
l, synaptic vesicle protein synthesis is not a prerequisite for the fo
rmation of new presynaptic-like terminals. We propose that preexisting
axonal components are reutilized to expedite presynaptic renewal as a
n early response to denervation/detargeting.