title: Two distinct subtypes of serotonergic fibers classified by co-expression with vesicular glutamate transporter 3 in rat forebrain.
abstract: Although virtually all of serotonin (5-HT) neurons in the midbrain raphe nuclei of rats are known to express vesicular glutamate transporter 3 (VGLUT3), VGLUT3-positive 5-HT fibers have been identified only in the cerebral cortex and hippocampus. Thus, our understanding of forebrain sites where 5-HT-glutamate interaction may be potentially managed by such possible glutamatergic 5-HT fibers themselves, is still largely fragmentary from a morphological point of view. To address this issue, we analyzed the rat forebrain by immunohistochemistry and chemical lesion experiment of 5-HT neurons by intracerebroventricular injection of a neurotoxin, 5,7-dihydroxytriptamine. Contrary to expectation, the double-label immunofluorescence staining revealed that the incidence of VGLUT3-positive 5-HT fibers is generally low over the forebrain, demonstrating occasional fibers with one or two double-labeled varicosities. The most extreme example was the nucleus of the lateral olfactory tract (LOT), which seemed to be devoid of double-labeled fibers despite high densities of 5-HT fibers and VGLUT3-positive fibers. In sharp contrast, robust plexuses of VGLUT3-positive 5-HT fibers were found in the dorsal, but not ventral, part of the lateral septum. The lesion experiment carried out to explore whether VGLUT3 exists in 5-HT fibers showed that in lesioned rats VGLUT3-positive fibers almost completely disappear from the septal region but seemed unchanged in the LOT. The present study shows that midbrain raphe-derived 5-HT fibers can be classified into two subtypes depending on co-expression with VGLUT3 staining in the forebrain.
authors.affiliation: Laboratory of Neuroendocrinology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. fshutoh@md.tsukuba.ac.jp
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Shutoh
authors.forename: Ayuka
authors.initials: A
authors.lastname: Ina
authors.forename: Sachine
authors.initials: S
authors.lastname: Yoshida
authors.forename: Jinko
authors.initials: J
authors.lastname: Konno
authors.forename: Setsuji
authors.initials: S
authors.lastname: Hisano
mesh_terms: D015116:5,7-Dihydroxytryptamine; D000818:Animals; D001369:Axons / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D001931:Brain Mapping; D003714:Denervation; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009498:Neurotoxins; D009833:Olfactory Pathways / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D009498:Neurotoxins; C482103:Slc17a8 protein, rat; D050496:Vesicular Glutamate Transport Proteins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin