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dc.contributor.authorPirri, Jennifer K.
dc.contributor.authorRayes, Diego
dc.contributor.authorAlkema, Mark J
dc.date2022-08-11T08:09:43.000
dc.date.accessioned2022-08-23T16:41:08Z
dc.date.available2022-08-23T16:41:08Z
dc.date.issued2015-09-08
dc.date.submitted2015-12-08
dc.identifier.citationPLoS Biol. 2015 Sep 8;13(9):e1002238. doi: 10.1371/journal.pbio.1002238. eCollection 2015.<a href="http://dx.doi.org/10.1371/journal.pbio.1002238">Link to article on publisher's site</a>
dc.identifier.issn1544-9173 (Linking)
dc.identifier.doi10.1371/journal.pbio.1002238
dc.identifier.pmid26348462
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39823
dc.description<p>First author Jennifer Pirri is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.</p>
dc.description.abstractBehavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the Caenorhabditis elegans escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26348462&dopt=Abstract">Link to Article in PubMed</a>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBehavioral Neurobiology
dc.titleA Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior
dc.typeJournal Article
dc.source.journaltitlePLoS biology
dc.source.volume13
dc.source.issue9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3624&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2620
dc.identifier.contextkey7920038
refterms.dateFOA2022-08-23T16:41:09Z
html.description.abstract<p>Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the Caenorhabditis elegans escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.</p>
dc.identifier.submissionpathoapubs/2620
dc.contributor.departmentGraduate School of Biomedical Sciences, Neuroscience Program
dc.contributor.departmentAlkema Lab
dc.contributor.departmentNeurobiology
dc.source.pagese1002238
dc.contributor.studentJennifer K. (Pirri) Ingemi
dc.description.thesisprogramNeuroscience


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