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J. Troy Littleton M.D., Ph.D.
Associate Professor of Biology

Department of Brain and Cognitive Sciences
Department of Biology
Building: 46-3243
Lab: Littleton Lab

The computational power of the brain
The computational power of the brain depends on synaptic connections that link together billions of neurons.  The focus of my laboratory's work is to understand the mechanisms by which neurons form synaptic connections, how synapses transmit information, and how synapses change during learning and memory.  To complement this basic research in neuroscience, we also study how alterations in neuronal signaling underlie several neurological diseases, including epilepsy and Huntington’s Disease. We combine molecular biology, protein biochemistry, electrophysiology, and imaging approaches with Drosophila genetics to address these questions.  Moving beyond genomic data to determine how proteins specify the distinctive signaling properties of neurons and enable them to interconnect into computational circuits that dictate behavior are major goals for the next decade of neuroscience research.  Despite the dramatic differences in complexity between Drosophila and humans, genomic analysis has confirmed that key neuronal proteins and the functional mechanisms they govern are remarkably similar.  As such, we are attempting to elucidate the mechanisms underlying synapse formation, function and plasticity using Drosophila as a model system. By characterizing how neurons integrate synaptic signals and modulate synaptic growth and strength, we hope to bridge the gap between molecular components of the synapse and the physiological responses they mediate. 

Selected Publications

Guan, Z., Saraswati, S., Adolfsen, B. & Littleton, J.T. (2005) Genome-wide transcriptional changes associated with enhanced activity in the Drosophila nervous system.  Neuron 48, 91-107.

Yoshihara, M., Adolfsen, B., Galle, K & Littleton J.T. (2005) Retrograde signaling by Syt 4 induces presynaptic release and synapse-specific growth.  Science 310, 858-863.

Montana, E.S. & Littleton, J.T. (2006) Expression profiling of a hypercontraction-induced myopathy in Drosophila suggests a compensatory cytoskeletal remodeling response. J. Biol. Chem. 281, 8100-8109.

Littleton, J.T. (2006) Mixing and matching during synaptic vesicle endocytosis.  Neuron 51, 149-151.

The Honey Bee Genome Sequencing Consortium (2006) Insights into social insects from the genome of the honeybee Apis mellifera Nature 443, 931-949.

Stilwell, G., Saraswati, S., Littleton, J.T. & Chouinard S.W. (2006) Development of a Drosophila seizure model for in vivo high-throughput drug screening. Eur. J. Neuroscience 24, 2211-2222.

Kimura, Y., Lee, W.C. & Littleton, J.T. (2007) Therapeutic prospects for the prevention of neurodegeneration in Huntington's Disease and the polyglutamine repeat disorders. Mini Rev. Med. Chem. 7, 99-106.

Barber, C. & Littleton, J. T. (2007) Synaptic Growth and Transcriptional Regulation in Drosophila, 253-275. In: Regulation of Transcription by Neuronal Activity, Ed. S. Dudek, Springer Science Publishing @2007.

Saraswati, S., Adolfsen, B. & Littleton, J.T. (2007) Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release.  PNAS 104, 14122-14127.

Mattaliano, M.D., Montana, E.S., Parisky, K., Littleton, J.T., Griffeth, L.C. (2007) The Drosophila ARC homolog regulates behavioral responses to starvation.  Molecular and Cellular Neuroscience 36, 211-221.

Huntwork, S. & Littleton, J.T. (2007) A complexin fusion clamp regulates spontaneous neurotransmitter release and synaptic growth.  Nature Neuroscience 10, 1235-1237.

Rodal, A.A. & Littleton, J.T. (2008) Synaptic endocytosis: Illuminating the role of clathrin assembly. Current Biology 18, 259-261.

Rodal, A.A., Motola-Barnes, R.N. & Littleton, J.T. (2008) Nervous Wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth.  J. Neuroscience 28, 8316-8325.

Zhang, S., Feany, M.B., Saraswati, S., Littleton, J.T. & Perrimon, N. (2009) Inactivation of Drosophila huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's Disease model.  Disease Models & Mechanisms, In Press.

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