My lab uses the Drosophila embryonic and larval motor system to study the development and function of motor circuits. Ultimately by understanding motor circuits from both of these perspectives we hope to gain a mechanistic understanding of the genetic basis of behavior.
My lab is interested in understanding how neural circuits implement motor programs that allow animals to move: How do microcircuits in the nerve cord control muscle contraction and locomotion? What is the functional architecture of the motor system at the cellular level? Using quantitative behavioral assays and muscle kinematics we define the functional relevance of several classes of evolutionarily-conserved interneurons (e.g., Even-skipped/Evx). Using a recently-completed transmission electron microscopic reconstruction of the entire Drosophila larval nervous system we define the network structure in which these neurons operate. Using optogenetics and calcium imaging we define how these networks operate in intact, behaving animals. These studies produce a better understanding of how neural circuits allow animals to move, provide insights relevant to nervous system evolution, and are requisites for understanding principles for circuit assembly.
My lab is also interested in understanding the developmental logic of how these motor circuits form. Specifically, we seek to understand how developmental history impacts circuit assembly--what is the role of lineage, temporal patterning, and transcriptional control in development? We currently use the EL sensorimotor circuit as model (Heckscher et al, 2015). As we identify additional circuits (described above) we will ask whether different motor circuits are assembled by similar or different developmental rules. This work has important implications for stem cell reprogramming that could be used to replace diseased/damaged neural tissue.
Heckscher, ES, Zarin, AA, Faumont, S, Clark, MC, Manning, LM, Fushiki, A, Schneider-Mizel, C, Fetter, RD, Truman, JW, Zwart, M, Landgraf, M, Cardona, A, Lockery, SR, Doe, CQ, (2015). Even-skipped+ interneurons are core components of a sensorimotor circuit that maintains left-right symmetric muscle contraction amplitude. Neuron. In press
Heckscher, ES, Long, F, Layden, MJ, Chuang, C, Manning, L, Richart, J, Pearson, JC, Crews, ST, Peng, H, Myers, E, Doe, CQ, (2014). Atlas-builder software and the eNeuro atlas: resources for developmental biology and neuroscience. Development. 141, 2524-2532. (PubMed)
Manning, L, Heckscher, ES, Purice, MD, Roberts, J, Bennett, AL, Kroll, JR, Pollard, JL, Strader, ME, Lupton, JR, Dyukareva, AV, Doan, PN, Bauer, D, Wilbur, A, Tanner, S. Kelly, JJ, Lai, S, Tran, KD, Kohwi, M, Laverty, TR, Pearson, JC, Crews, ST, Rubin, GM, Doe, CQ, (2012). Annotated embryonic CNS expression patterns of 5000 GMR GAL4 lines: a resource for manipulating gene expression and analyzing cis-regulatory motifs. Cell Rep. 2, 1002-13. (PubMed)
Heckscher, ES, Lockery, SR, Doe, CQ, (2012). Characterization of Drosophila larval crawling at the level of organism, segment, and somatic body wall musculature. J. Neurosci. 32, 12460-12471. (PubMed)
Heckscher, ES, Fetter, RD, Marek, KW, Albin, SD, Davis, GW, (2007). NF-kappaB, IkappaB and IRAK control glutamate receptor abundance at the Drosophila NMJ. Neuron. 55, 859-873. (PubMed)
For a complete list of my published work click here.