Alterations in neuronal signaling underlie a variety of forms of synaptic plasticity associated with learning and memory, and have important roles in pathological states such as epilepsy, Alzheimer's disease, Parkinson's disease and the genetically complex neuropsychiatric disorders. With the completion of the C. elegans, Drosophila and human genome sequences, neurobiologists for the first time are able to examine the complete set of ion channels and synaptic proteins that govern neural function. Interpreting this wealth of sequence data to understand how these proteins specify the distinctive signaling properties of individual neurons and enable them to interconnect into complex computational circuits that ultimately dictate behavior will be major goals for the next decade.

The focus of our laboratory is to elucidate the molecular mechanisms underlying synapse formation, function and plasticity. We are combining molecular biology, protein biochemistry, electrophysiology, electron microscopy, and imaging approaches with Drosophila genetics to investigate the molecular mechanisms involved in neuronal signaling. We are using current genetic approaches to identify and characterize novel temperature-sensitive paralytic mutants, which will be used as a tool to identify and study new components of neuronal signaling pathways. Many of these temperature-sensitive paralytic mutations alter synaptic sprouting, membrane excitability or synaptic transmission, properties that give us insights into the roles of these gene products in synapse formation, synaptic plasticity and epilepsy. DNA microarrays are being used to identify activity-regulated genes in our temperature-sensitive seizure mutants to understand the downstream molecular events resulting from increased neuronal activity.

Using reverse genetic approaches, we are elucidating the structure-function of known synaptic proteins such as: Drosophila synaptotagmin and SNARE families involved in transmitter release, and the calcium channel and NMDA receptor superfamilies. Genetics, electrophysiology and fluorescence resonance energy transfer spectroscopy are being employed to understand the role of these components in synaptic function. Drosophila, expressing wild-type and mutant forms of human huntingtin, is being used as a model of Huntington's disease.

Selected Publications:

Littleton, J.T., Sereno T.L., Rubin, G.M., Ganetzky, B. & Chapman E.R. (1999) Synaptic function modulated by changes in the ratio of synaptotagmin I and IV. Nature 400:757-600.

Littleton, J.T. & Ganetzky, B. (2000) Ion Channels and Synaptic Organization: Analysis of the Drosophila Genome. Neuron 26, 35-43.

Littleton, J.T., Vyas, B., Bai, J., Desai, R.C., Garment, M.B., Carlson, S.D., Ganetzky, B. & Chapman, E.R. (2001) synaptotagmin mutants reveal essential functions for the C2B-domain in Ca2+-triggered fusion and recycling of synaptic vesicles. J. Neuroscience, 21:1421-1433.


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Confocal reconstruction of the Drosophila brain immunostained for synaptotagmin.

Assistant Professor, Departments of Biology and Brain and Cognitive Sciences

J. Troy Littleton received his MD and Ph.D. from the Baylor College of Medicine. He completed his postdoctoral training at the University of Wisconsin. In 2000, he joined the faculty of the Department of Biology and the Picower Center for Learning and Memory at MIT. Dr. Littleton is the recipient of the Searle Scholar Award, an Alfred P. Sloan Foundation Fellowship, and the MIT School of Science Poitras Scholar Award in Neuroscience.

laboratory webpage