How do neural circuits guide our behavior? The answers promise to revolutionize our understanding of what it means to be human and how to repair the damaged neural circuits that underlie human neurological and psychiatric disorders. The incredible complexity of the mammalian brain, however, coupled with limited ability to genetically manipulate specific neural circuits in vertebrates, has made our progress difficult. My lab is developing new approaches that will rejuvenate this effort. We take advantage of the fact that many basic neural computations are evolutionarily ancient: invertebrates are capable of some of the same computations that humans are. This enables us to study processes familiar to vertebrate physiologists using the fruit fly, an animal with a relatively simple, genetically hard-wired nervous system. As a model genetic system, Drosophila offers a complex, interesting behavioral repertoire combined with an extensive toolkit for both forward and reverse genetic analysis. Our goal is to provide a complete mechanistic understanding of how visual information is processed at the level of identified cells and circuits. In preliminary work, we have developed new behavioral paradigms that allow high-throughput, automated forward genetic screens to identify neurons specifically involved in such processes as motion detection and color perception. To define the behavioral contributions of these functionally important neurons, we are adapting analytical techniques from ion channel biophysics and systems neuroscience to the analysis of fly behavior. Using new molecular and electrophysiological techniques that we will develop, we propose to link circuit anatomy to circuit function, and to define how changes in the activities of functionally important neurons lead to behavioral decisions. These studies will provide the first synthesis linking a sensory input to a behavioral output, through the functions of specific molecules, neurons and circuits.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
NIH Director’s Pioneer Award (NDPA) (DP1)
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Special Emphasis Panel (ZGM1-NDPA-G (P2))
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Wehrle, Janna P
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Stanford University
Schools of Medicine
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Velez, Mariel M; Gohl, Daryl; Clandinin, Thomas R et al. (2014) Differences in neural circuitry guiding behavioral responses to polarized light presented to either the dorsal or ventral retina in Drosophila. J Neurogenet 28:348-60
Behnia, Rudy; Clark, Damon A; Carter, Adam G et al. (2014) Processing properties of ON and OFF pathways for Drosophila motion detection. Nature 512:427-30
Gohl, Daryl M; Freifeld, Limor; Silies, Marion et al. (2014) Large-scale mapping of transposable element insertion sites using digital encoding of sample identity. Genetics 196:615-23
Wernet, Mathias F; Klovstad, Martha; Clandinin, Thomas R (2014) A Drosophila toolkit for the visualization and quantification of viral replication launched from transgenic genomes. PLoS One 9:e112092
Velez, Mariel M; Wernet, Mathias F; Clark, Damon A et al. (2014) Walking Drosophila align with the e-vector of linearly polarized light through directed modulation of angular acceleration. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 200:603-14
Silies, Marion; Gohl, Daryl M; Fisher, Yvette E et al. (2013) Modular use of peripheral input channels tunes motion-detecting circuitry. Neuron 79:111-27
Clark, Damon A; Freifeld, Limor; Clandinin, Thomas R (2013) Mapping and cracking sensorimotor circuits in genetic model organisms. Neuron 78:583-95
Freifeld, Limor; Clark, Damon A; Schnitzer, Mark J et al. (2013) GABAergic lateral interactions tune the early stages of visual processing in Drosophila. Neuron 78:1075-89
Gao, Xiaojing J; Potter, Christopher J; Gohl, Daryl M et al. (2013) Specific kinematics and motor-related neurons for aversive chemotaxis in Drosophila. Curr Biol 23:1163-72
Wernet, Mathias F; Velez, Mariel M; Clark, Damon A et al. (2012) Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila. Curr Biol 22:12-20

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