title: Distribution of serotonin receptor 5-HT6 mRNA in rat neuronal subpopulations: A double in situ hybridization study.
abstract: The 5-HT6 receptor (5-HT6R) is almost exclusively expressed in the brain and has emerged as a promising target for cognitive disorders, including Alzheimer's disease. In the present study, we have determined the cell types on which the 5-HT6R is expressed by colocalizing 5-HT6R mRNA with that of a range of neuronal and interneuronal markers in the rat brain. Here, we show that 5-HT6R mRNA was expressed at high levels in medium spiny neurons in caudate putamen and in nucleus accumbens, as well as in the olfactory tubercle. Striatal 5-HT6R mRNA was colocalized with both dopamine D1 and D2 receptor mRNA. 5-HT6R mRNA was moderately expressed in the hippocampus and throughout cortical regions in glutamatergic neurons coexpressing vGluT1. A subset of GAD67-positive GABAergic interneurons (approximately 15%) expressed 5-HT6R mRNA in the cortex and hippocampus, the majority of which belonged to the 5-HT3a receptor (5-HT3aR)-expressing subpopulation. In contrast, 5-HT6R mRNA was only expressed to a minor extent in the parvalbumin and somatostatin subpopulations. A subset of calbindin- and calretinin-positive GABAergic interneurons expressed 5-HT6R mRNA while only a very minor fraction of VIP or NPY interneurons in forebrain structures expressed 5-HT6R mRNA. Serotonergic, dopaminergic or cholinergic neurons did not express 5-HT6R mRNA. These data indicate that the 5-HT6R is located on GABAergic and glutamatergic principal neurons, and on a subset of interneurons mainly belonging to the 5-HT3aR subgroup suggesting that the 5-HT6R is positioned to regulate the balance between excitatory and inhibitory signaling in the brain. These data provide new insights into the mechanisms of 5-HT6R signaling.
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: lohe@lundbeck.com.
authors.forename: L
authors.initials: L
authors.lastname: Helboe
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: jege@lundbeck.com.
authors.forename: J
authors.initials: J
authors.lastname: Egebjerg
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: idj@lundbeck.com.
authors.forename: I E M
authors.initials: IE
authors.lastname: de Jong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D007395:Interneurons / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000032:analysis; D011985:Receptors, Serotonin / Q000032:analysis*
chemical_list: D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor
keywords: 5-HT(6) receptor; Alzheimer’s disease; in situ hybridization; interneuron; pyramidal cell; rat