Potential for Chemolithoautotrophy Among Ubiquitous Bacteria Lineages in the Dark Ocean Brandon K Swan et al Science 333 1296 2011 DOI 10 1126 science 1203690 This copy is for your personal non commercial use only If you wish to distribute this article to others you can order high quality copies for your colleagues clients or customers by clicking here The following resources related to this article are available online at www sciencemag org this infomation is current as of September 19 2011 Updated information and services including high resolution figures can be found in the online version of this article at http www sciencemag org content 333 6047 1296 full html Supporting Online Material can be found at http www sciencemag org content suppl 2011 08 31 333 6047 1296 DC1 html A list of selected additional articles on the Science Web sites related to this article can be found at http www sciencemag org content 333 6047 1296 full html related This article cites 32 articles 13 of which can be accessed free http www sciencemag org content 333 6047 1296 full html ref list 1 This article appears in the following subject collections Genetics http www sciencemag org cgi collection genetics Geochemistry Geophysics http www sciencemag org cgi collection geochem phys Science print ISSN 0036 8075 online ISSN 1095 9203 is published weekly except the last week in December by the American Association for the Advancement of Science 1200 New York Avenue NW Washington DC 20005 Copyright 2011 by the American Association for the Advancement of Science all rights reserved The title Science is a registered trademark of AAAS Downloaded from www sciencemag org on September 19 2011 Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here consumption varies continuously with the level of AGRP neuron activation nearly full suppression of activity is required to block the evoked feeding response 28 AGRP neurons in Agrp cre mice 29 were transduced using a bicistronic Cre recombinase Cre dependent viral vector 30 Fig 4A AGRP neurons coexpressing ChR2 and PSAML141F Y115FGlyR Fig 4B could be activated with light and were reversibly silenced by PSEM89S during photostimulation in brain slices Fig 4 C and D Mice coexpressing ChR2 and PSAML141F Y115F GlyR or expressing ChR2 alone in AGRP neurons ate voraciously in response to photostimulation after intraperitoneal i p saline injection and for each mouse this consumption was used as the baseline for subsequent treatments After i p administration of PSEM89S photostimulation evoked feeding was strongly suppressed in mice expressing PSAML141F Y115F GlyR but not in mice expressing only ChR2 Fig 4 E and F Twenty four hours later photostimulation evoked food intake recovered to baseline levels two way analysis of variance one factor repeated measure TPSEM89S F1 9 12 9 P 0 006 TPSAML141F Y115F GlyR F1 9 1 3 P 0 30 interaction F1 9 22 4 P 0 001 Fig 4 E and F Moreover after photostimulation Fos a marker of neuron activation 31 was almost completely suppressed in ChR2 expressing neurons from mice administered PSEM89S fig S14 Thus PSAML141F Y115F GlyR and PSEM89S constitute an effective neuronal silencer system in vivo even for strong synchronous depolarizing currents that result from ChR2 photoactivation Our results show how concerted chemical and genetic engineering of a complex ligand binding interface can be used to develop pharmacologically selective actuators and small molecule effectors for construction of a LGIC toolbox PSEMs the agonists for the resulting ion channels act rapidly in the brain after peripheral delivery Together these components enable combinatorial construction fig S15 of cell type selective tools to control a range of conductances which can be used to activate or silence neurons These ion channels could be further elaborated by applying extensive structure function relationships in Cys loop receptors including mutations that modify 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