title: Preprodynorphin-expressing neurons constitute a large subgroup of somatostatin-expressing GABAergic interneurons in the mouse neocortex.
abstract: Dynorphins, leumorphin, and neoendorphins are preprodynorphin (PPD)-derived peptides and ligands for κ-opioid receptors. Using an antibody to PPD C-terminal, we investigated the chemical and molecular characteristics of PPD-expressing neurons in mouse neocortex. PPD-immunopositive neuronal somata were distributed most frequently in layer 5 and less frequently in layers 2-4 and 6 throughout neocortical regions. Combined labeling of immunofluorescence and fluorescent mRNA signals revealed that almost all PPD-immunopositive neurons expressed glutamic acid decarboxylase but not vesicular glutamate transporter, indicating their γ-aminobutyric acid (GABA)ergic characteristics, and that PPD-immunopositive neurons accounted for 15% of GABAergic interneurons in the primary somatosensory area. As GABAergic interneurons were divided into several groups by specific markers, we further examined the chemical characteristics of PPD-expressing neurons by the double immunofluorescence labeling method. More than 95% of PPD-immunopositive neurons were also somatostatin (SOM)-immunopositive in the primary somatosensory, primary motor, orbitofrontal, and primary visual areas, but only 24% were SOM-immunopositive in the medial prefrontal cortex. In the primary somatosensory area, PPD-immunopositive neurons constituted 50%, 79%, 55%, and 17% of SOM-immunopositive neurons in layers 2-3, 4, 5, and 6, respectively. Although SOM-expressing neurons contained calretinin-, neuropeptide Y-, nitric oxide synthase-, and reelin-expressing neurons as subgroups, only reelin immunoreactivity was detected in many PPD-immunopositive neurons. These results indicate that PPD-expressing neurons constitute a large subgroup of SOM-expressing cortical interneurons, and the PPD/SOM-expressing GABAergic neurons might serve not only as inhibitory elements in the local cortical circuit, but also as modulators for cortical neurons expressing κ-opioid and/or SOM receptors.
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan; Research Fellow of Japan Society for the Promotion of Science (JSPS), Tokyo, 102-8472, Japan.
authors.forename: Jaerin
authors.initials: J
authors.lastname: Sohn
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hioki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002452:Cell Count; D004399:Dynorphins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; D000091042:Reelin Protein; D050496:Vesicular Glutamate Transport Proteins; C036448:pre-prodynorphin; D013004:Somatostatin; D004399:Dynorphins; D019001:Nitric Oxide Synthase; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase
keywords: GABAergic neuron; combined labeling of immunofluorescence and fluorescent mRNA signals; double immunofluorescence labeling; opioid peptide; somatostatin