Howard Hughes Medical Institute, UC-Berkeley, Department of Molecular and Cell Biology, LSA # 519, Berkeley, CA, 94720, USA. # present address: Friedrich-Miescher Laboratorium der Max-Planck Gesellschaft, Spemannstrasse 37 - 39, 72076 Tübingen, Germany.
Activity-dependent plasticity plays a major role in controlling
the fine tuning and remodeling of synaptic connections during
development and adult life. In systems as diverse as Aplysia and
rat independent lines of research have suggested the importance
of cAMP signaling cascades and cell adhesion molecules in these
processes of synaptic plasticity.
Here we demonstrate that synaptic plasticity at the Drosophila
neuromuscular junction (NMJ) is controlled by activity- and cAMP-
dependent mechanisms at two levels: Functional synaptic
changes are regulated by CREB-dependent gene expression, and
structural synaptic alterations are controlled by the cell
adhesion molecule Fasciclin II (Fas II). Specifically we found
that increased neuronal activity and cAMP-levels in the mutants
eag,Sh and dunce downregulate synaptic Fas II-levels. This synaptic
Fas II regulation is necessary and sufficient to mediate
increased junctional sprouting in both mutants. However, Fas II
controlled junctional sprouting itself is not sufficient to alter
synaptic strength. We found that the induction of CREB activator-
and blocker-isoforms can alter synaptic output without changing
the junctional structure. We further demonstrate that CREB
mediated functional changes and Fasciclin II controlled junctional
sprouting cooperate to alter synaptic strength.