{"id":14774,"date":"2018-08-02T17:56:17","date_gmt":"2018-08-02T17:56:17","guid":{"rendered":"https:\/\/drugprevent.org.uk\/ppp\/?p=14774"},"modified":"2018-11-01T19:14:04","modified_gmt":"2018-11-01T19:14:04","slug":"%ce%b2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling","status":"publish","type":"post","link":"https:\/\/drugprevent.org.uk\/ppp\/2018\/08\/%ce%b2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling\/","title":{"rendered":"\u03b2-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling"},"content":{"rendered":"<p style=\"text-align: justify;\"><span style=\"font-family: verdana, geneva, sans-serif; font-size: 10pt; color: #0000ff;\">Abstract<\/span><br \/>\n<span style=\"font-family: verdana, geneva, sans-serif; font-size: 10pt; color: #0000ff;\">\u03b1- and \u03b2-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that although \u03b2-neurexins are expressed at much lower levels than \u03b1-neurexins, conditional knockout of \u03b2-neurexins with continued expression of \u03b1-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The \u03b2-neurexin knockout phenotype was attenuated by CB1-receptor inhibition which blocks presynaptic endocannabinoid signaling or by 2-arachidonoylglycerol synthesis inhibition which impairs postsynaptic endocannabinoid release. In synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum neurons, presynaptic\u00a0in vivo\u00a0knockout of \u03b2-neurexins aggravated endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP; presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol synthesis inhibition again reversed this block. Moreover, conditional knockout of \u03b2-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our data suggest that presynaptic \u03b2-neurexins control synaptic strength in excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis, revealing an unexpected role for \u03b2-neurexins in the endocannabinoid-dependent regulation of neural circuits.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-family: verdana, geneva, sans-serif; font-size: 10pt; color: #0000ff;\">Source:\u00a0 <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4709013\/\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4709013\/<\/a><\/span><\/p>\n<p><span style=\"color: #0000ff; font-family: verdana, geneva, sans-serif; font-size: 10pt;\">See also:<\/span><\/p>\n<p><span style=\"color: #0000ff; font-family: verdana, geneva, sans-serif; font-size: 10pt;\"><a style=\"color: #0000ff;\" href=\"https:\/\/drugprevent.org.uk\/ppp\/2018\/08\/endocannabinoid-mediates-excitatory-synaptic-function-of-%ce%b2-neurexins-commentary-%ce%b2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling\/\">https:\/\/drugprevent.org.uk\/ppp\/2018\/08\/endocannabinoid-mediates-excitatory-synaptic-function-of-%ce%b2-neurexins-commentary-%ce%b2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling\/<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Abstract \u03b1- and \u03b2-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that although \u03b2-neurexins are expressed at much lower levels than \u03b1-neurexins, conditional knockout of \u03b2-neurexins with continued expression of \u03b1-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The \u03b2-neurexin knockout phenotype was attenuated by CB1-receptor inhibition [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[30,64,106],"tags":[],"class_list":["post-14774","post","type-post","status-publish","format-standard","hentry","category-cannabis-marijuana","category-health","category-medical-studies-papers"],"_links":{"self":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts\/14774","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/comments?post=14774"}],"version-history":[{"count":0,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts\/14774\/revisions"}],"wp:attachment":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/media?parent=14774"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/categories?post=14774"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/tags?post=14774"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}