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My lab is combining electrophysiology, genetics and molecular biology in Drosophila to examine the structure, function and development of neural circuits. We use targeted expression of genes to identified sensory neurons in order to block the function or alter the development of synaptic circuits. For example, targeted expression of the anatomical marker lacZ reveals the structure of sensory neurons and the timing of axon growth into the nervous system while targeted expression of tetanus toxin to these same sensory neurons reveals their function by removing them from the circuit. |
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We have adapted standard electrophysiological techniques to Drosophila in order to assess the neural function directly by targeting toxins to subsets of sensory neurons, blocking synaptic transmission and exploring the consequences for reflex function and behavior. We then use these results and these methods to examine the assembly process and its disruption by various mutations. For example, we have discovered that mutations in cytoplasmic motors like the dynein complex affect axon growth and ultimately synaptic connectivity. We are in the process of determining how these cytoplasmic motors disrupt axon growth and synaptic connectivity by following their development during metamorphosis. Finally, we are determining how mutations in cytoplasmic motors disrupt synaptic connections using intracellular recording.
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Murphey, R. K. and T. A. Godenschwege (2002). "New roles for ubiquitin
in the assembly
and function of neuronal circuits." Neuron 36(1): 5-8.
Godenschwege, T. A., H. Hu, X. Shan-Crofts, C. S. Goodman and R. K. Murphey
(2002).
"Bi-directional signaling by Semaphorin 1a during central synapse formation
in
Drosophila." Nat Neurosci 5(12): 1294-301.
Godenschwege, T. A., J. H. Simpson, X. Shan, G. J. Bashaw, C. S. Goodman
and R. K.
Murphey (2002). "Ectopic expression in the giant fiber system of Drosophila
reveals
distinct roles for roundabout (Robo), Robo2, and Robo3 in dendritic guidance
and
synaptic connectivity." J Neurosci 22(8): 3117-29.
Allen, M.J., X. Shan and R.K. Murphey (2000). A role for Drosophila Drac1 in neurite outgrowth and synaptogenesis in the giant fiber system. Molecular and Cellular Neuroscience. Mol Cell Neuroscience 16; 754-765.
Allen, M.J., X. Shan, P. Caruccio, S. Froggett and R.K. Murphey. (1999). Targeted expression of truncated Glued disrupts giant fiber synapse formation in Drosophila. J. Neurosci. 19, 9374-9384.
Murphey, R.K., Caruccio, P.C., Getzinger, M., Westgate, P., Phillis, R. (1999) Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: a role of retrograde motors. Dev. Biol. 209(1), 86-97.
Jin, P., Griffith, L., Murphey, R.K. (1998). Presynaptic calcium-calmodulin dependent protein kinase II regulates habituation of a simple reflex in adult Drosophila. J. Neurosci. (in press).