title: Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex.
abstract: Gamma-aminobutyric acid (GABA)ergic neurons in the neocortex have been mainly regarded as interneurons and thought to provide local interactions. Recently, however, glutamate decarboxylase (GAD) immunocytochemistry combined with retrograde labeling experiments revealed the existence of GABAergic projection neurons in the neocortex. We further studied the network of GABAergic projection neurons in the neocortex by using GAD67-green fluorescent protein (GFP) knock-in mice for retrograde labeling and a novel neocortical GABAergic neuron labeling method for axon tracing. Many GFP-positive neurons were retrogradely labeled after Fast Blue injection into the primary somatosensory, motor and visual cortices. These neurons were labeled not only around the injection site, but also at a long distance from the injection site. Of the retrogradely labeled GABAergic neurons remote from the injection sites, the vast majority (91%) exhibited somatostatin immunoreactivity, and were preferentially distributed in layer II, layer VI and in the white matter. In addition, most of GABAergic projection neurons were positive for neuropeptide Y (82%) and neuronal nitric oxide synthase (71%). We confirmed the long-range projections by tracing GFP-labeled GABAergic neurons with axon branches traveled rostro-caudally and medio-laterally. Axon branches could be traced up to 2 mm. Some (n = 2 of 4) were shown to cross the areal boundaries. The GABAergic projection neurons preferentially received neocortical inputs. From these results, we conclude that GABAergic projection neurons are distributed throughout the neocortex and are part of a corticocortical network.
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Tomioka
authors.forename: Keiko
authors.initials: K
authors.lastname: Okamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Furuta
authors.forename: Fumino
authors.initials: F
authors.lastname: Fujiyama
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tamamaki
mesh_terms: D000818:Animals; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000737:chemistry* / Q000378:metabolism; D009434:Neural Pathways / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1