Genetic dissection of structural and functional components of synaptic plasticity. III. CREB is necessary for presynaptic functional plasticity.
Increased cAMP (in dunce mutants) leads to an increase in the structure and function of the Drosophila neuromuscular junction. Synaptic Fasciclin II (Fas II) controls this structural plasticity, but does not alter synaptic function. Here, we show that CREB, the cAMP response element-binding protein, acts in parallel with Fas II to cause an increase in synaptic strength. Expression of the CREB repressor (dCREB2-b) in the dunce mutant blocks functional but not structural plasticity. Expression of the CREB activator (dCREB2-a) increases synaptic strength only in FasII mutants that increase bouton number. This CREB-mediated increase in synaptic strength is due to increased presynaptic transmitter release. Expression of dCREB2-a in a FasII mutant background genetically reconstitutes this cAMP-dependent plasticity. Thus, cAMP initiates parallel changes in CREB and Fas II to achieve long-term synaptic enhancement.
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
G W
GW
Davis
C M
CM
Schuster
C S
CS
Goodman
D000818:Animals; D030801:Animals, Genetically Modified; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D005071:Evoked Potentials; D015870:Gene Expression; D007814:Larva; D008564:Membrane Potentials; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D012097:Repressor Proteins / Q000096:biosynthesis; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D015534:Trans-Activators / Q000096:biosynthesis
D015816:Cell Adhesion Molecules, Neuronal; C102181:CrebB protein, Drosophila; D017362:Cyclic AMP Response Element-Binding Protein; D029721:Drosophila Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C051642:fasciclin II; D000242:Cyclic AMP