Joshua Kaplan Laboratory
Work in the Kaplan lab is focused on understanding how signals in the brain lead to particular patterns of behavior. We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C. elegans.
Signals in the brain occur at specialized intercellular connections, known as synapses. There is a surprising amount of diversity in the structural and functional characteristics of synapses. Some synapses are large, others are small. Some are strong others are weak. Very little is known about the molecular differences that underlie this diversity in synaptic function. Our goal is to define the cell biological mechanisms by which synapses are made different from each other.
G protein regulation of synaptic transmission: We showed that two G proteins (Go and Gq) antagonistically regulate neurotransmitter release at a particular set of C. elegans synapses, and that these G proteins directly regulate several aspects of synaptic vesicle recycling. Current projects aim to identify downstream targets of these G proteins, and to determine the mechanisms by which they act.
Synapse formation and trafficking of synaptic proteins: The brain is an exceedingly complex circuit that somehow maintains the specificity of connections made between cells and of the signals transmitted at these connections. For example, a typical hippocampal neuron has 11,000 synaptic inputs, comprising at least 10 different neurotransmitters. Clearly, chaos would ensue if neurotransmitter receptors were randomly targeted to all synapses made by this cell. We have developed methods for visualizing individual synapses in living worms. Using these methods, we identified several genes that regulate synapse formation, targeting of receptors to synapses, and the abundance of receptors at each synapse.