Abstract
Over the past 30 years, people have learned a great deal about the specification and connectivity of motor neurons to their target body wall muscles. To determine how these motor neurons are used to generate larval locomotion, it is essential to identify the interneurons in the locomotor circuits. To identify interneurons required for larval behavior, including locomotion, people have identified several hundred Gal4 lines expressed in 1–5 interneurons (Manning et al., 2012, Cell Reports), and are using these lines to screen for interneurons regulating different aspects of larval behavior. The speaker expressed the warmth-activated TrpA1 channel in each “sparse interneuron Gal4 line” and identified lines with behavioral defects such as reverse locomotion, turning only, feeding only, left-right uncoordinated, pausing, and rigid paralysis (in collaboration with Matt Clark, in press). He has investigated one phenotype in detail (left-right incoordination), showing that the affected interneurons are Even-skipped (Eve)+ contralateral ascending interneurons (conserved in mouse; Evx1/2). He has also used thermogenetics and optogenetics to determine the function of these interneurons in larval locomotion and a TEM (transmission electron microscopy) serial reconstruction of the entire larval CNS to identify pre- and postsynaptic partners to define a proprioceptive sensorimotor circuit containing these neurons (Heckscher et al., 2015, Neuron). The characterization of interneurons in other phenotypic categories is in progress. In addition, the speaker is using the circuits he identified as an entry point for understanding how developmental mechanisms lead to circuit formation: e.g. whether neurons in a circuit share a progenitor of origin, birth-order, or transcription factor code. Future directions include studying plasticity and compensation within these circuits, the role of astrocytes in establishment or maintenance of the circuits, as well as their remodeling and participation in adult locomotor circuits.
About the speaker
Prof Chris Doe received his PhD in Developmental Neurobiology from Stanford University in 1987. He was Assistant Professor and then Associate Professor of Cell and Structural Biology at the University of Illinois at Urbana-Champaign. He joined the University of Oregon in 1998, and is currently Professor of Institute of Neuroscience. He is also an Investigator in the Howard Hughes Medical Institute.
Prof Doe’s research focuses on neural stem cells, cell polarity and CNS development in Drosophila. His current research focus is on characterizing genes that regulate temporal identity within neuroblast lineages, and identifying mechanisms of neural circuit formation for larval locomotion.
Prof Doe received numerous awards including the International Human Frontier Science Program Award (1992), Oregon Medical Research Foundation Discovery Award (2011) and the US National Institutes of Health MERIT Award (2013). He is also elected a Fellow of the American Association for the Advancement of Science in 1999 and the American Academy of Arts & Sciences in 2014.
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