title: Cellular architecture and transmitter phenotypes of neurons of the mouse median raphe region.
abstract: The median raphe region (MRR, which consist of MR and paramedian raphe regions) plays a crucial role in regulating cortical as well as subcortical network activity and behavior, while its malfunctioning may lead to disorders, such as schizophrenia, major depression, or anxiety. Mouse MRR neurons are classically identified on the basis of their serotonin (5-HT), vesicular glutamate transporter type 3 (VGLUT3), and gamma-aminobutyric acid (GABA) contents; however, the exact cellular composition of MRR regarding transmitter phenotypes is still unknown. Using an unbiased stereological method, we found that in the MR, 8.5 % of the neurons were 5-HT, 26 % were VGLUT3, and 12.8 % were 5-HT and VGLUT3 positive; whereas 37.2 % of the neurons were GABAergic, and 14.4 % were triple negative. In the whole MRR, 2.1 % of the neurons were 5-HT, 7 % were VGLUT3, and 3.6 % were 5-HT and VGLUT3 positive; whereas 61 % of the neurons were GABAergic. Surprisingly, 25.4 % of the neurons were triple negative and were only positive for the neuronal marker NeuN. PET-1/ePET-Cre transgenic mouse lines are widely used to specifically manipulate only 5-HT containing neurons. Interestingly, however, using the ePET-Cre transgenic mice, we found that far more VGLUT3 positive cells expressed ePET than 5-HT positive cells, and about 38 % of the ePET cells contained only VGLUT3, while more than 30 % of 5-HT cells were ePET negative. These data should facilitate the reinterpretation of PET-1/ePET related data in the literature and the identification of the functional role of a putatively new type of triple-negative neuron in the MRR.
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.|János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, 1085, Hungary.
authors.forename: Katalin E
authors.initials: KE
authors.lastname: Sos
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.
authors.forename: Márton I
authors.initials: MI
authors.lastname: Mayer
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Cserép
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.
authors.forename: Flóra S
authors.initials: FS
authors.lastname: Takács
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.|János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, 1085, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Szőnyi
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary.
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary. nyiri.gabor@koki.mta.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nyiri
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D065847:Dorsal Raphe Nucleus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D059326:Serotonergic Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D012701:Serotonin; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C504941:Slc17a8 protein, mouse
keywords: 5-HT; Immunohistochemistry; Median raphe; PET-1; Paramedian raphe; Serotonin; Stereology; VGAT; VGLUT3; ePET