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Topography and transmitter phenotype of the projections between the lateral habenula, the rostromedial tegmental nucleus and the dorsal raphe nucleus in the rat

Grant number: 12/02388-3
Support type:Regular Research Grants
Duration: June 01, 2012 - May 31, 2014
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Martin Andreas Metzger
Grantee:Martin Andreas Metzger
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Chemutai Sego ; Leandro Bueno Lima


Aversive events impose a threat on brain and body homeostasis, creating a state known as stress. Pathological stress can lead to major depression and anxiety. Brain regions activated in stress involve on one hand telencephalic structures coping with the perception and coding of stress and on the other hand structures in the midbrain and mesopontine tegmentum modulating output systems that prepare the stress response. Interposed between these systems is the lateral habenula (LHb), a predominantly glutamatergic epithalamic structure, which receives major inputs from output structures of the basal telencephalon and projects to monoaminergic cell groups in the midbrain and mesopontine tegmentum. The LHb is selectively activated by aversive stimuli and predictive signals of negative errors and its basal activity is altered by physiological and pathological stress. The LHb exerts a profound inhibition over mesencephalic dopamine neurons, an effect mediated by a GABAergic relay in the mesopontine tegmetum, recently denominated rostromedial tegmental nucleus (RMTg). Interestingly, the RMTg also exerts a prominent inhibition over serotonergic neurons in the dorsal raphe nucleus (DR) and there is anatomical evidence that this effect is also mediated by the RMTg. However, almost nothing is known about the exact topography of RMTg projections to the DR and the neurotransmitters used by the projection neurons in the RMTg and target neurons in the DR. Postulating that the RMTg might be an important relay between the LHb and the DR we pretend to investigate in the present project using neuronal tracing techniques combined with immunohistochemical and in situ hybridization methods the exact topography and transmitter phenotype of the projections between the LHb, RMTg, and DR. (AU)

Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FURIGO, ISADORA C.; MELO, HELEN M.; LYRA E SILVA, NATALIA M.; RAMOS-LOBO, ANGELA M.; TEIXEIRA, PRYSCILA D. S.; BUONFIGLIO, DANIELLA C.; WASINSKI, FREDERICK; LIMA, ELIANA R.; HIGUTI, ELIZA; PERONI, CIBELE N.; BARTOLINI, PAOLO; SOARES, CARLOS R. J.; METZGER, MARTIN; DE FELICE, FERNANDA G.; DONATO, JR., JOSE. Brain STAT5 signaling modulates learning and memory formation. Brain Structure & Function, v. 223, n. 5, p. 2229-2241, JUN 2018. Web of Science Citations: 9.
METZGER, MARTIN; BUENO, DEBORA; LIMA, LEANDRO B. The lateral habenula and the serotonergic system. Pharmacology Biochemistry and Behavior, v. 162, n. SI, p. 22-28, NOV 2017. Web of Science Citations: 20.
LIMA, LEANDRO B.; BUENO, DEBORA; LEITE, FERNANDA; SOUZA, STEFANI; GONCALVES, LUCIANO; FURIGO, ISADORA C.; DONATO, JR., JOSE; METZGER, MARTIN. Afferent and efferent connections of the interpeduncular nucleus with special reference to circuits involving the habenula and raphe nuclei. JOURNAL OF COMPARATIVE NEUROLOGY, v. 525, n. 10, p. 2411-2442, JUL 1 2017. Web of Science Citations: 17.
DA SILVA, EDUARDO SIMAO; FLORES, RAFAEL APPEL; RIBAS, ANDERSON SAVARIS; TASCHETTO, ANA PAULA; FARIA, MOACIR SERRALVO; LIMA, LEANDRO BUENO; METZGER, MARTIN; DONATO, JR., JOSE; PASCHOALINI, MARTA APARECIDA. Injections of the of the alpha(1)-adrenoceptor antagonist prazosin into the median raphe nucleus increase food intake and Fos expression in orexin neurons of free-feeding rats. Behavioural Brain Research, v. 324, p. 87-95, MAY 1 2017. Web of Science Citations: 1.
FURIGO, ISADORA C.; METZGER, MARTIN; TEIXEIRA, PRYSCILA D. S.; SOARES, CARLOS R. J.; DONATO, JR., JOSE. Distribution of growth hormone-responsive cells in the mouse brain. Brain Structure & Function, v. 222, n. 1, p. 341-363, JAN 2017. Web of Science Citations: 13.
LIMA, LEANDRO B.; METZGER, MARTIN; FURIGO, ISADORA C.; DONATO, JR., J. Leptin receptor-positive and leptin receptor-negative proopiomelanocortin neurons innervate an identical set of brain structures. Brain Research, v. 1646, p. 366-376, SEP 1 2016. Web of Science Citations: 7.
FURIGO, ISADORA C.; KIM, KI WOO; NAGAISHI, VANESSA S.; RAMOS-LOBO, ANGELA M.; DE ALENCAR, AMANDA; PEDROSO, JOAO A. B.; METZGER, MARTIN; DONATO, JR., JOSE. Prolactin-sensitive neurons express estrogen receptor-alpha and depend on sex hormones for normal responsiveness to prolactin. Brain Research, v. 1566, p. 47-59, MAY 30 2014. Web of Science Citations: 23.
SEGO, CHEMUTAI; GONCALVES, LUCIANO; LIMA, LEANDRO; FURIGO, ISADORA C.; DONATO, JR., JOSE; METZGER, MARTIN. Lateral Habenula and the Rostromedial Tegmental Nucleus Innervate Neurochemically Distinct Subdivisions of the Dorsal Raphe Nucleus in the Rat. JOURNAL OF COMPARATIVE NEUROLOGY, v. 522, n. 7, p. 1454-1484, MAY 1 2014. Web of Science Citations: 53.

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