Molecular mechanisms that regulate synaptic efficacy at the Drosophila neuromuscular junction

The homeostatic regulation of synaptic efficacy is a mechanism by which the nervous system maintains stability despite changes in cellular excitability that occur during development or various types of plasticity. The Drosophila neuromuscular junction (NMJ) has been used as a model glutamatergic synapse to study two types of homeostatic compensation. The first involves the regulation of synaptic efficacy by increasing postsynaptic glutamate receptor function in response to defects in presynaptic neurotransmitter release. The second type of homeostatic compensation involves the retrograde regulation of presynaptic neurotransmitter release in response to decreases in postsynaptic muscle excitability. This work describes experiments that further characterize the molecular mechanisms that underlie the regulation of postsynaptic receptors and presynaptic neurotransmitter release.;The p21-activated kinase (Pak) signaling pathway has been described as a regulator of postsynaptic glutamate receptor abundance at the NMJ. Here we examine how postsynaptic Pak signaling controls glutamate receptor abundance. In addition, we identify a second genetically separable function of Pak signaling which controls muscle membrane development. Pak signaling is thus required postsynaptically for the coordination of multiple aspects of postsynaptic maturation.;To understand the dynamics of glutamate receptor trafficking at the NMJ, we describe the creation of a modified glutamate receptor subunit that is capable of binding fluorescently conjugated alpha-bungarotoxin. alpha-bungarotoxin should only bind surface receptors, and by imaging tagged glutamate receptors over time we can visualize the internalization and insertion of these receptors into the membrane.;The molecular mechanisms underlying the retrograde control of presynaptic neurotransmitter release at the NMJ are not well understood. Here we describe the identification of the first known inhibitor of synaptic homeostasis. Identification of the pathways through which this inhibitor act may eventually lead to a greater understanding of the mechanisms that regulate homeostasis.