cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons

Abstract

Summary: The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons. : Maiellaro et al. find that local cAMP controls site-specific synaptic plasticity in Drosophila motor neurons. The expression of a genetically encoded fluorescent cAMP sensor in motor neurons allows visualization of local cAMP signals and gives insight into the formation of cAMP signaling microdomains. Keywords: cAMP, synaptic plasticity, PDE, octopamine, FRET, active zone, dunce, GPCR