The125th KARC Colloquium


Date&Time 5 July 2016(Tue) 15:00-16:30
Place TV conference room 2, 3F, Research Building 1, Advanced ICT Research Institute
Lecturer Genetic Dissection of Neurotransmitter Release at Drosophila Synapses
Speaker J. Troy Littleton
Professor Picower Institute for Learning and Memory at MIT
Abstract The computational power of the brain depends on synaptic connections that link together billions of neurons. With the long-term goal of understanding how synaptic signaling regulates neuronal communication and connectivity, we have used Drosophila as a model system to characterize the molecular mechanisms underlying neurotransmitter release and synaptic growth and plasticity. Neurotransmitters can be released during evoked fusion following an action potential, or through spontaneous fusion of vesicles (termed “minis”) in the absence of nerve stimulation. The two modes of vesicle release have been found at most synapses and are assumed to occur across the same population of active zones, though this has been difficult to define using classical approaches. A major limitation for the study of neurotransmitter release has been the inability to examine vesicle fusion at individual active zones. Electrophysiological studies of synaptic transmission measure the postsynaptic effect of neurotransmitter release over a large population of release sites, precluding an analysis of how individual active zones participate in and regulate synaptic vesicle fusion. We have now developed transgenic tools that allow Ca2+ imaging of postsynaptic glutamate receptor activation following vesicle fusion to spatially visualize exocytotic events occurring through both spontaneous and evoked release pathways, allowing us to define general rules for vesicle fusion events at single active zones. Our data indicate a majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. Indeed, a subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Using these new transgenic tools to visualize single active zone exocytosis, we are characterizing how single release sites work, how they undergo plasticity, and how they contribute to both evoked and spontaneous fusion. In addition, we are defining the molecular machines that regulate both evoked and spontaneous transmission across synapses.
Language English
Admission Free