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Schoppik, David

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Schoppik

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David

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Schoppik, David

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2012 - 20132

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Author's Publications: search.filters.isAuthorOfPublication.b29dc4b0-6ca1-45bc-b3d6-23d4d4af8b3c

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    Optical Control of Metabotropic Glutamate Receptors
    (2013) Levitz, Joshua; Pantoja, Carlos; Gaub, Benjamin; Janovjak, Harald; Reiner, Andreas; Hoagland, Adam; Schoppik, David; Kane, Brian; Stawski, Philipp; Schier, Alexander; Trauner, Dirk; Isacoff, Ehud Y.
    G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.
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    The Tangential Nucleus Controls a Gravito-inertial Vestibulo-ocular Reflex
    (Elsevier, 2012) Bianco, Isaac; Ma, Leung-Hang; Schoppik, David; Robson, Drew; Orger, Michael B.; Beck, James C.; Li, Jennifer; Schier, Alexander; Engert, Florian; Baker, Robert
    Whilst adult vertebrates sense changes in head position using two classes of accelerometer, at larval stages zebrafish lack functional semicircular canals and rely exclusively on their otolithic organs to transduce vestibular information. Despite this limitation, they perform an effective vestibulo-ocular reflex (VOR) that serves to stabilize gaze in response to pitch and roll tilts. Using single-cell electroporations and targeted laser-ablations, we identified a specific class of central vestibular neurons, located in the tangential nucleus, which are essential for the utricle-dependent VOR. Tangential nucleus neurons project contralaterally to extraocular motoneurons, and in addition, to multiple sites within the reticulospinal complex. We propose that tangential neurons function as a broadband inertial accelerometer, processing utricular acceleration signals to control the activity of extraocular and postural neurons, thus completing a fundamental three-neuron circuit responsible for gaze stabilization.