cally in Fig. 5 where vesicles move from microtubule to microfilament transport systems at the base of the spine. The management of this putative transition remains to be determined because a thin cortical layer of actin filaments is also present within dendrite shafts. The mechanisms responsible for delivering materials via the spine cytoplasm to sites in the postsynaptic junction have significant implications for synaptic plasticity in view of growing evidence for physical exchange of receptor molecules in the postsynaptic membrane of glutamatergic synapses (69–72).
The necessity of special mechanisms for transferring materials from shaft to spine raises the question of why such a partitioning of dendrite structure should exist at all. One possibility, suggested by the results of the present study, is that this separation is a specialization for regulating anatomical plasticity. As our time-lapse recordings show, the actin and microtubule domains are associated with distinct rates of plasticity. Whereas actin in dendritic spine defines a region of rapid morphological change occurring over seconds and minutes (14, 15, 17), time-lapse imaging of MAP2 suggests that microtubules in the dendrite shaft undergo little change in periods of up to 3 h. This does not exclude that dynamic changes in dendritic microtubules may occur over longer periods. Indeed time-lapse imaging of MAP2-containing microtubule bundles in transfected epithelial cells shows that gradual alterations in the configuration of the microtubule cytoskeleton can occur over periods of several hours (33). This finding suggests that MAP2-containing neuronal microtubules may have a capacity for morphological plasticity although at a rate intrinsically slower than that of actin filament arrays, which appear constantly motile in comparable recordings (14). That gradual changes in the extent and branching of dendrites can occur has been demonstrated by repetitive imaging of dendrites in superior cervical ganglia of adult rats where substantial changes in dendritic arbors have been documented over periods of weeks and months (73, 74). However, other studies support the idea that dendritic spines are the predominant site of activity-dependent morphological plasticity in the brain in vivo (for example, refs. 17 and 75–78).
Taken together these observations suggest that microdifferentiation of the dendritic cytoskeleton in mature neurons may be a cellular specialization for dividing the structural support of dendrites into two levels of stability. One of these, involving microtubules, appears to respond slowly, providing morphological stability to dendrite arbors while still allowing for long-term flexibility, whereas the other, involving motile actin filaments, allows for rapid, activity-dependent changes in synaptic structure.
We thank Thierry Doll and Jean-Francois Spetz for assistance in preparing transgenic animals.
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