"Regulation of synaptic strength at the Drosophila neuromuscular junction"
The glutamatergic Drosophila neuromuscular junction (NMJ) offers a simple model system to study synaptic transmission and development. We set out to learn more about how synaptic strength and growth are regulated at the NMJ by using a genetically encoded fluorescent calcium sensor, which is targeted to postsynaptic densities. This sensor, called SynapCam, reports on calcium entering through postsynaptic glutamate receptors after synaptic transmission, on the level of a single bouton and single impulse. Using SynapCam to image synaptic transmission, we have discovered that there is a gradient of synaptic strength at muscle 6 from weak proximal to strong distal boutons (1) (left panel of figure). I have found that the production of strong distal boutons is disrupted in mutants of the Bone Morphogenic Protein (BMP) signaling pathway (right panel of figure), which has previously been shown to regulate synaptic growth at the NMJ. Strong connections correlate with the presence of microtubule loops in the boutons, suggesting a role for microtubule organization in distributing transmission strength. Mutations that disrupt microtubule organization disrupt the transmission gradient, supporting this interpretation. We propose that the BMP pathway, shown previously to function in the homeostatic regulation of axon growth, also functions to boost synaptic transmission in a spatially selective manner by organizing the microtubule system.
1. Guerrero G, Reiff DF, Agarwal G, Ball RW, Borst A, Goodman CS, Isacoff EY. Heterogeneity in synaptic transmission along a Drosophila larval motor axon. 2005. Nature Neuroscience 8: 1188-1196
This figure shows results from SynapCam recordings in a wildtype larva (left) and in a mutant for the Type II BMP receptor (right). Red indicates that the sensor gave a large response, so these synapses are stronger than those that are in blue. The green insets are HRP stains that show the structure of the axons. The asterisks indicate the distal boutons, whereas the arrows indicate where the axon enters the NMJ (proximal boutons). Notice that the end bouton gives the biggest response in wildtype, but the gradient is disrupted in the mutant.