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Processing of aversive stimuli: circuitry between the laterodorsal tegmental nucleus, the habenula, and dorsal and median raphe nuclei

Grant number: 17/16473-6
Support type:Regular Research Grants
Duration: October 01, 2017 - September 30, 2019
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:Jose Donato Junior


The habenula (Hb) is an epithalamic structure differentiated into medial (MHb) and lateral habenula (LHb). The LHb plays a key role in encoding disappointments and expectation of punishments, whereas the MHb-interpeduncular nucleus (IP) axis is critically involved in the mediation of the aversive effects of nicotine. Consistent with a key role in processing aversive information, the Hb has been implicated in a broad array of functions and pathologic conditions, notably in mechanisms of stress, nicotine consumption and in the pathophysiology of anxiety and depression. So far, the vast majority of research on the Hb has focused on its role in regulating monoaminergic nuclei. Thus, there is now ample evidence that MHb/LHb are robustly interconnected with dopamine and serotonin nuclei by a complex network of direct and indirect connections. In contrast, little is known about the relations of MHb/LHb with cholinergic cell groups such as the laterodorsal tegmental nucleus (LDTg). The LDTg is an important component of the ascending reticular system and has been implicated in mechanisms of fear/anxiety and the promotion of emotional arousal under adverse conditions. In order to clarify Hb connections with the LDTg, the main objective of the present project is to investigate in detail the topography and neurochemical signature of the direct projections between LHb e LDTg, as well as the circuits that interconnect the LDTg with midline structures such as the MHb-IP axis, the dorsal/median raphe nuclei, and the septum. For this purpose we will combine tract tracing methods with immunohistochemical/in situ hybridization techniques and genetic approaches. (AU)

Scientific publications (7)
(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)
QUARESMA, PAULA G. F.; DOS SANTOS, WILLIAN O.; WASINSKI, FREDERICK; METZGER, MARTIN; DONATO JR, JOSE. Neurochemical phenotype of growth hormone-responsive cells in the mouse paraventricular nucleus of the hypothalamus. JOURNAL OF COMPARATIVE NEUROLOGY, SEP 2020. Web of Science Citations: 0.
CAMPOS, ANA M. P.; TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO, JR., JOSE. Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis. Journal of Neuroendocrinology, AUG 2020. Web of Science Citations: 1.
BUENO, DEBORA; LIMA, LEANDRO B.; SOUZA, RUDIERI; GONCALVES, LUCIANO; LEITE, FERNANDA; SOUZA, STEFANI; FURIGO, ISADORA C.; DONATO, JR., JOSE; METZGER, MARTIN. Connections of the laterodorsal tegmental nucleus with the habenular-interpeduncular-raphe system. JOURNAL OF COMPARATIVE NEUROLOGY, v. 527, n. 18, p. 3046-3072, DEC 15 2019. Web of Science Citations: 2.
METZGER, MARTIN; SOUZA, RUDIERI; LIMA, LEANDRO B.; BUENO, DEBORA; GONCALVES, LUCIANO; SEGO, CHEMUTAI; DONATO, JR., JOSE; SHAMMAH-LAGNADO, SARA J. Habenular connections with the dopaminergic and serotonergic system and their role in stress-related psychiatric disorders. European Journal of Neuroscience, DEC 2019. Web of Science Citations: 0.
LIMA, LEANDRO B.; PEDROSO, JOAO A. B.; METZGER, MARTIN; GAUTRON, LAURENT; DONATO, JR., JOSE. Relationship of alpha-MSH and AgRP axons to the perikarya of melanocortin-4 receptor neurons. Brain Research, v. 1717, p. 136-146, AUG 15 2019. Web of Science Citations: 0.
FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; DE SOUZA, GABRIEL O.; COUTO, GISELE C. L.; GARCIA ROMERO, GUADALUPE; PERELLO, MARIO; FRAZAO, RENATA; ELIAS, LUCILA L.; METZGER, MARTIN; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO, JR., J. Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons. NATURE COMMUNICATIONS, v. 10, FEB 8 2019. Web of Science Citations: 10.
LIMA, LEANDRO BUENO; HAUBENTHAL, FERNANDA TAIS; SILVEIRA, MARINA AUGUSTO; BOHLEN, TABATA MARIZ; METZGER, MARTIN; DONATO JR, JOSE; FRAZAO, RENATO. Conspecific odor exposure predominantly activates non-kisspeptin cells in the medial nucleus of the amygdala. Neuroscience Letters, v. 681, p. 12-16, AUG 10 2018. Web of Science Citations: 3.

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