title: VGluT3-expressing CCK-positive basket cells construct invaginating synapses enriched with endocannabinoid signaling proteins in particular cortical and cortex-like amygdaloid regions of mouse brains.
abstract: Invaginating synapses in the basal amygdala are a unique type of GABAergic synapses equipped with molecular-anatomical organization specialized for 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling. Cholecystokinin (CCK)-positive basket cell terminals protrude into pyramidal cell somata and form invaginating synapses, where apposing presynaptic and postsynaptic elements are highly loaded with cannabinoid receptor CB₁ or 2-AG synthetic enzyme diacylglycerol lipase-α (DGLα), respectively. The present study scrutinized their neurochemical and neuroanatomical phenotypes in adult mouse telencephalon. In the basal amygdala, vesicular glutamate transporter-3 (VGluT3) was transcribed in one-fourth of CB₁-expressing GABAergic interneurons. The majority of VGluT3-positive CB₁-expressing basket cell terminals apposed DGLα clusters, whereas the majority of VGluT3-negative ones did not. Importantly, VGluT3-positive basket cell terminals selectively constructed invaginating synapses. GABAA receptors accumulated on the postsynaptic membrane of invaginating synapses, whereas metabotropic glutamate receptor-5 (mGluR₅) was widely distributed on the somatodendritic surface of pyramidal cells. Moreover, CCK₂ receptor (CCK₂R) was highly transcribed in pyramidal cells. In cortical regions, pyramidal cells equipped with such VGluT3/CB₁/DGLα-accumulated invaginating synapses were found at variable frequencies depending on the subregions. Therefore, in addition to extreme proximity of CB₁- and DGLα-loaded presynaptic and postsynaptic elements, tripartite transmitter phenotype of GABA/glutamate/CCK is the common neurochemical feature of invaginating synapses, suggesting that glutamate, CCK, or both can promote 2-AG synthesis through activating Gαq/₁₁ protein-coupled mGluR₅ and CCK₂R. These molecular configurations led us to hypothesize that invaginating synapses might be evolved to provide some specific mechanisms of induction, regulation, and cooperativity for 2-AG-mediated retrograde signaling in particular cortical and cortex-like amygdaloid regions.
authors.affiliation: Departments of Anatomy, Psychiatry, and.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omiya
authors.affiliation: Departments of Anatomy.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.affiliation: Departments of Anatomy.
authors.forename: Kohtarou
authors.initials: K
authors.lastname: Konno
authors.affiliation: Departments of Anatomy.
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Departments of Anatomy.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Psychiatry, and.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.affiliation: Departments of Anatomy, watamasa@med.hokudai.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000679:Amygdala / Q000166:cytology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D002766:Cholecystokinin; D063388:Endocannabinoids; D005968:Glutamate Decarboxylase; D008071:Lipoprotein Lipase; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043887:Receptor, Cholecystokinin B; C504941:Slc17a8 protein, mouse; C402565:glutamate decarboxylase 1
keywords: amygdala; cannabinoid CB1 receptor; cerebral cortex; cholecystokinin-positive basket cell; invaginating synapse; sn-1-specific diacylglycerol lipase