title: ON and OFF retinal ganglion cells differentially regulate serotonergic and GABAergic activity in the dorsal raphe nucleus.
abstract: The dorsal raphe nucleus (DRN), the major source of serotonergic input to the forebrain, receives excitatory input from the retina that can modulate serotonin levels and depressive-like behavior. In the Mongolian gerbil, retinal ganglion cells (RGCs) with alpha-like morphological and Y-like physiological properties innervate the DRN with ON DRN-projecting RGCs out numbering OFF DRN-projecting RGCs. The DRN neurons targeted by ON and OFF RGCs are unknown. To explore retino-raphe anatomical organization, retinal afferents labeled with Cholera toxin B were examined for association with the postsynaptic protein PSD-95. Synaptic associations between retinal afferents and DRN serotonergic and GABAergic neurons were observed. To explore retino-raphe functional organization, light-evoked c-fos expression was examined. Light significantly increased the number of DRN serotonergic and GABAergic cells expressing c-Fos. When ON RGCs were rendered silent while enhancing the firing rate of OFF RGCs, c-Fos expression was greatly increased in DRN serotonergic neurons suggesting that OFF DRN-projecting RGCs predominately activate serotonergic neurons whereas ON DRN-projecting RGCs mainly target GABAergic neurons. Direct glutamatergic retinal input to DRN 5-HT neurons contributes to the complex excitatory drive regulating these cells. Light, via the retinoraphe pathway can modify DRN 5-HT neuron activity which may play a role in modulating affective behavior.
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Anatomy, School of Basic Medical Sciences, Peking University, Beijing, 100191 PR China.|Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing, 100191 PR China.|Key Laboratory for Visual Impairment and Restoration (Ministry of Education), Peking University, Beijing, 100191 PR China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Pu
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583 USA.|Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198 USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Pickard
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.|Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, PR China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.|Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, PR China.|GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou 510632, PR China.|Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, PR China.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Ren
mesh_terms: D000344:Afferent Pathways; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000378:metabolism; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D054351:Electrical Synapses; D018683:Excitatory Amino Acid Agents / Q000378:metabolism; D059330:GABAergic Neurons / Q000502:physiology*; D005786:Gene Expression Regulation; D005849:Gerbillinae; D006801:Humans; D055537:Light Signal Transduction; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000502:physiology*; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D018683:Excitatory Amino Acid Agents; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D002772:Cholera Toxin