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

• Grant number: 17/16473-6
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2017
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Martin Andreas Metzger
• Grantee: Martin Andreas Metzger
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Jose Donato Junior

Abstract

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

(16)

(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)

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. (12/12202-4, 14/08755-3, 17/16473-6, 17/02983-2, 15/14588-5)

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. (17/02983-2, 17/16473-6, 16/09679-4)

METZGER, MARTIN; SOUZA, RUDIERI; LIMA, LEANDRO B.; BUENO, DEBORA; GONCALVES, LUCIANO; SEGO, CHEMUTAI; DONATO, JOSE, JR.; SHAMMAH-LAGNADO, SARA J.. Habenular connections with the dopaminergic and serotonergic system and their role in stress-related psychiatric disorders. European Journal of Neuroscience, v. 53, n. 1, p. 24-pg., 2019-12-27. (17/16473-6, 17/02983-2)

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.; et al. Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons. NATURE COMMUNICATIONS, v. 10, FEB 8 2019. (16/09679-4, 17/16473-6, 17/05007-4, 17/04006-4, 17/02983-2, 17/21840-8)

FLORES, RAFAEL APPEL; STEINBACH, RENATA; PEDROSO, JOAO A. B.; METZGER, MARTIN; DONATO, JR., JOSE; PASCHOALINI, MARTA APARECIDA. Injections of the alpha-2 adrenoceptor agonist clonidine into the dorsal raphe nucleus increases food intake in satiated rats. Neuropharmacology, v. 182, JAN 2021. (17/16473-6, 17/02983-2, 12/15517-6)

MOINHO, TAIS M.; TAVARES, MARIANA R.; CAMPOS, ANA M. P.; FRAZAO, RENATA; METZGER, MARTIN; DONATO, JOSE, JR.. Simple method to induce denaturation of fluorescent proteins in free-floating brain slices. JOURNAL OF NEUROSCIENCE METHODS, v. 371, p. 10-pg., 2022-02-15. (19/21707-1, 20/01318-8, 20/10102-9, 17/16473-6)

SOUZA, RUDIERI; BUENO, DEBORA; LIMA, LEANDRO B.; MUCHON, MARIA J.; GONCALVES, LUCIANO; DONATO, JOSE, JR.; SHAMMAH-LAGNADO, SARA J.; METZGER, MARTIN. Top-down projections of the prefrontal cortex to the ventral tegmental area, laterodorsal tegmental nucleus, and median raphe nucleus. Brain Structure & Function, v. 227, n. 7, p. 23-pg., 2022-07-22. (20/01318-8, 17/16473-6)

CAMPOS, ANA M. P.; TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO, JOSE, JR.. 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, v. 32, n. 9, p. 11-pg., 2020-08-24. (16/02224-1, 17/17998-5, 16/20897-3, 17/02983-2, 17/16473-6)

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. (16/20897-3, 16/02224-1, 17/16473-6, 17/02983-2, 17/17998-5)

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, v. 53, n. 1, SI, DEC 2019. (17/02983-2, 17/16473-6)

WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO JR, JOSE. Distribution of growth hormone-responsive cells in the brain of rats and mice. Brain Research, v. 1751, JAN 15 2021. (16/20897-3, 16/02224-1, 17/16473-6, 17/17998-5, 17/02983-2)

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. (17/02983-2, 17/16473-6)

DE SOUZA, GABRIEL O.; CHAVES, FERNANDA M.; SILVA, JOSIANE N.; PEDROSO, JOAO A. B.; METZGER, MARTIN; FRAZAO, RENATA; DONATO JR, JOSE. Gap junctions regulate the activity of AgRP neurons and diet-induced obesity in male mice. Journal of Endocrinology, v. 255, n. 2, p. 16-pg., 2022-11-01. (21/11551-4, 19/21707-1, 17/21854-9, 20/01318-8, 17/16473-6)

DONATO, JR., JOSE; WASINSKI, FREDERICK; FURIGO, ISADORA C.; METZGER, MARTIN; FRAZAO, RENATA. Central Regulation of Metabolism by Growth Hormone. CELLS, v. 10, n. 1, JAN 2021. (20/01318-8, 16/09679-4, 19/21707-1, 16/20897-3, 17/16473-6)

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, v. 529, n. 6, SEP 2020. (17/02983-2, 16/20897-3, 17/25281-3, 17/16473-6)

CAMPOS, ANA M. P.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO JR, JOSE. Fasting reduces the number of TRH immunoreactive neurons in the hypothalamic paraventricular nucleus of male rats, but not in mice. Neuroscience Letters, v. 752, MAY 1 2021. (16/02224-1, 17/16473-6, 17/17998-5, 16/20897-3)