{"id":879,"date":"2018-11-16T12:28:56","date_gmt":"2018-11-16T17:28:56","guid":{"rendered":"https:\/\/pjenkinslab.org\/?p=879"},"modified":"2024-03-14T11:34:22","modified_gmt":"2024-03-14T16:34:22","slug":"andrews-paper-accepted-for-publication-in-molecular-psychiatry","status":"publish","type":"post","link":"https:\/\/pjenkinslab.org\/index.php\/2018\/11\/16\/andrews-paper-accepted-for-publication-in-molecular-psychiatry\/","title":{"rendered":"Andrew&#8217;s paper accepted for publication in Molecular Psychiatry!"},"content":{"rendered":"\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-fu653-fa947bda4708ac979d528273554aba6f\">\n.flex_column.av-fu653-fa947bda4708ac979d528273554aba6f{\n-webkit-border-radius:0px 0px 0px 0px;\n-moz-border-radius:0px 0px 0px 0px;\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div class='flex_column av-fu653-fa947bda4708ac979d528273554aba6f av_one_third  avia-builder-el-0  el_before_av_two_third  avia-builder-el-first  first flex_column_div av-zero-column-padding '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-jool3ujr-9f030648ff7034a048bd641739ec8c48\">\n.avia-image-container.av-jool3ujr-9f030648ff7034a048bd641739ec8c48 img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-jool3ujr-9f030648ff7034a048bd641739ec8c48 .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-jool3ujr-9f030648ff7034a048bd641739ec8c48 av-styling- avia-align-center  avia-builder-el-1  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" class='wp-image-880 avia-img-lazy-loading-not-880 avia_image ' src=\"https:\/\/pjenkinslab.org\/wp-content\/uploads\/2018\/11\/MolPsych.jpg\" alt='' title='MolPsych'  height=\"398\" width=\"300\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/pjenkinslab.org\/wp-content\/uploads\/2018\/11\/MolPsych.jpg 300w, https:\/\/pjenkinslab.org\/wp-content\/uploads\/2018\/11\/MolPsych-226x300.jpg 226w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/div><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-7grtz-65537d86fe0a97f6ab170f7e9b776a8a\">\n.flex_column.av-7grtz-65537d86fe0a97f6ab170f7e9b776a8a{\n-webkit-border-radius:0px 0px 0px 0px;\n-moz-border-radius:0px 0px 0px 0px;\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div class='flex_column av-7grtz-65537d86fe0a97f6ab170f7e9b776a8a av_two_third  avia-builder-el-2  el_after_av_one_third  avia-builder-el-last  flex_column_div av-zero-column-padding '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-jool2ms0-4138ab99f09746e12ea4851ea50c93db\">\n#top .av_textblock_section.av-jool2ms0-4138ab99f09746e12ea4851ea50c93db .avia_textblock{\nfont-size:18px;\n}\n<\/style>\n<section  class='av_textblock_section av-jool2ms0-4138ab99f09746e12ea4851ea50c93db'  itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" ><p>Andrew&#8217;s paper &#8220;Ankyrin-G Regulates Forebrain Connectivity and Network Synchronization via Interaction with GABARAP&#8221; has been accepted for publication in <em>Molecular Psychiatry<\/em>! This collaborative work gives important insight into the effects of <em>ANK3<\/em> dysfunction on forebrain network activity, with strong implications for bipolar disorder.\u00a0GABAergic circuits are critical for the synchronization and higher order function of brain networks, and defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons where it interacts directly with the GABA<sub>A<\/sub>\u00a0receptor associated protein (GABARAP) to stabilize cell surface GABA<sub>A<\/sub>\u00a0receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G\/GABARAP interaction (<em>Ank3<\/em> W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that <em>Ank3<\/em> W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the <em>ANK3<\/em> W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how <em>ANK3<\/em> loss-of-function variants may contribute to human disease. Congratulations to Andrew and all of our collaborators on this project!<\/p>\n<p>You can see the online published version <a href=\"https:\/\/doi.org\/10.1038\/s41380-018-0308-x\">here.\u00a0<\/a><\/p>\n<\/div><\/section><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":882,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/posts\/879"}],"collection":[{"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/comments?post=879"}],"version-history":[{"count":7,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/posts\/879\/revisions"}],"predecessor-version":[{"id":1364,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/posts\/879\/revisions\/1364"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/media\/882"}],"wp:attachment":[{"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/media?parent=879"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/categories?post=879"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/pjenkinslab.org\/index.php\/wp-json\/wp\/v2\/tags?post=879"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}