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the presynaptic nerve (Yee and Pestronk, 1987), e.g. by preventing the assembly of adhesive complexes at the presynaptic terminal. Presynaptic modulation of anatomical plasticity through mTOR1 and/or proteasome-mediated degradation pathways would provide for further flexibility in how individual presynaptic nerves exhibit anatomical plasticity in their target regions.

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There is evidence to suggest that the principles for regulation of anatomical plasticity in the target region revealed in this study might also apply to circuit assembly and plasticity in the CNS. Thus: 1) coordinate regulation of sprouting and synapse remodeling by synaptic activity and postsynaptic differentiation has been reported for the assembly of circuits during development (Ruthazer et al., 2003, Zou and Cline, 1999); 2) slowly developing anatomical plasticity has been demonstrated in the adult as a result of chronic functional alterations (Bareyre et al., 2004, Darian-Smith and Gilbert, 1994). We find that the requirements for anatomical plasticity in the adult can vary among individual postsynaptic targets (e.g. LGC^DeSyn versus SOL^DeSyn), and that at some systems pronounced rearrangements in local connectivity take place in the presence of synaptic activity (e.g. hippocampal mossy fiber terminals (Galimberti et al., 2006)). The results of this study might thus provide a general conceptual frame- work to investigate the relative roles of intrinsic postsynaptic factors, synapse-assem- bling mechanisms and synaptic activity in locally regulating anatomical plasticity in the target region.

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time sprouts are not associated with ectopic AChR clusters. b, In vivo time-lapse imaging of nerves and AChR clusters in BotA-treated LGC^DeSyn and RF^FaSyn. Note gradual elongation of sprouts (indicated by separate numbers) on LGC^DeSyn, changing patterns of ectopic AChR clusters along sprout-1, and absence of clusters at distal ends of most sprouts. For orientation, a red arrowhead marks the same LGC^DeSyn NMJ in the panels; small arrows (+16d, AChR, LGC^DeSyn) indicate examples of two ectopic clusters that were not detectable at day +14. See text for a more detailed de- scription of these data. Bars: 50 μm.

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