title: Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat.
abstract: The lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR-projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin-rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well-acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)-nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR.
authors.affiliation: Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900, São Paulo, Brazil; Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-900, São Paulo, Brazil.
authors.forename: Chemutai
authors.initials: C
authors.lastname: Sego
authors.forename: Luciano
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Leandro
authors.initials: L
authors.lastname: Lima
authors.forename: Isadora C
authors.initials: IC
authors.lastname: Furigo
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
authors.forename: Martin
authors.initials: M
authors.lastname: Metzger
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D019262:Habenula / Q000033:anatomy & histology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011903:Raphe Nuclei / Q000033:anatomy & histology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology* / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C482103:Slc17a8 protein, rat; D050496:Vesicular Glutamate Transport Proteins; D012701:Serotonin; D005680:gamma-Aminobutyric Acid
keywords: Raphe nuclei; reward; serotonin, glutamate, anxiety; stress