Neurobiological substrates of the medial prefrontal cortex functional lateralization on defensive reactions induced by social defeat stress in mice

• Grant number: 17/25409-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2018
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Ricardo Luiz Nunes de Souza
• Grantee: Ricardo Luiz Nunes de Souza
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Stress situations are risk factors for the development of mental disorders. However, not everyone exposed to a stressor develops such disorders, probably because each subject displays distinct degrees of susceptibility or resilience phenotypes to stress. The search for the neural systems underlying these phenotypes has highlighted the medial prefrontal cortex (mPFC) and, more recently, its functional laterality. In brief, previous studies have shown that the exposure to chronic stress provokes morphofunctional differences in the left and right mPFC, culminating in persistent maladaptive changes. In this context, the functional laterality of mPFC seems to be involved in the expression of phenotypes in the presence of aversive situations, emphasizing how important is the mapping of the projections emitted by this structure and the characterization of the activation pattern of the areas that receive these afferences, using neuronal tracers and immunohistochemistry for ”FosB, respectively. Furthermore, changes in the ”FosB transcription factors and the involvement of glutamatergic neurotransmission have also been pointed out as fundamental for the expression of such phenotypes. In the present study, we also intend to clarify these parameters in stressed animals. Considering the neuroanatomical, functional and behavioral profiles produced by chronic stress, this study will investigate whether chemical inactivation (provoked with local injection of N-methyl-d-aspartate - NMDA) of the left mPFC is able to mimick partially or totally the stress effects, rendering animals more susceptible to stressors. Thus, this study attempts to clarify the functional laterality of mPFC on the modulation of anxiety- and depressant-like responses, particularly emphasizing the role of glutamatergic neurotransmission in the expression of distinct behavioral phenotypes (susceptible x resilient) in mice exposed to a social defeat paradigm. (AU)

Scientific publications

(8)

(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)

SILVEIRA, LARA MARIA; TAVARES, LIGIA RENATA RODRIGUES; BAPTISTA-DE-SOUZA, DANIELA; CARMONA, ISABELA MIRANDA; DE OLIVEIRA, PAULO EDUARDO CARNEIRO; NUNES-DE-SOUZA, RICARDO LUIZ; CANTO-DE-SOUZA, AZAIR. Anterior cingulate cortex, but not amygdala, modulates the anxiogenesis induced by living with conspecifics subjected to chronic restraint stress in male mice. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 16, p. 16-pg., 2023-01-06. (17/25409-0, 15/00006-4)

SANTOS-COSTA, NATHALIA; BAPTISTA-DE-SOUZA, DANIELA; CANTO-DE-SOUZA, LUCAS; DA COSTA, VINICIUS FRESCA; NUNES-DE-SOUZA, RICARDO LUIZ. Glutamatergic Neurotransmission Controls the Functional Lateralization of the mPFC in the Modulation of Anxiety Induced by Social Defeat Stress in Male Mice. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 15, AUG 23 2021. (17/25409-0, 16/24568-4, 16/08665-0)

BENASSI-CEZAR, GIOVANA; CARMONA, ISABELA MIRANDA; BAPTISTA-DE-SOUZA, DANIELA; NUNES-DE-SOUZA, RICARDO LUIZ; CANTO-DE-SOUZA, AZAIR. Differential modulation of the anterior cingulate and insular cortices on anxiogenic-like responses induced by empathy for pain. Neuropharmacology, v. 192, JUL 1 2021. (17/25409-0, 15/00006-4)

RODRIGUES TAVARES, LIGIA RENATA; PELARIN, VINICIUS; BAPTISTA-DE-SOUZA, DANIELA; PEREIRA FERRARI, DANIELE; NUNES-DE-SOUZA, RICARDO LUIZ; CANTO-DE-SOUZA, AZAIR. 5-HT3 receptor within the amygdaloid complex modulates pain hypersensitivity induced by empathy model of cohabitation with a partner in chronic pain condition in mice. Social Neuroscience, JUL 2021. (12/22238-6, 17/25409-0, 15/15335-3)

FARIA, M. P.; LAVERDE, C. F.; NUNES-DE-SOUZA, R. L.. Anxiogenesis induced by social defeat in male mice: Role of nitric oxide, NMDA, and CRF1 receptors in the medial prefrontal cortex and BNST. Neuropharmacology, v. 166, APR 2020. (17/25409-0)

BAPTISTA-DE-SOUZA, DANIELA; RODRIGUES TAVARES, LIGIA RENATA; CANTO-DE-SOUZA, LUCAS; NUNES-DE-SOUZA, RICARDO LUIZ; CANTO-DE-SOUZA, AZAIR. Behavioral, hormonal, and neural alterations induced by social contagion for pain in mice. Neuropharmacology, v. 203, FEB 1 2022. (16/08665-0, 17/25409-0, 15/00006-4)

VICTORIANO, GABRIEL; SANTOS-COSTA, NATHALIA; MASCARENHAS, DIEGO CARDOZO; NUNES-DE-SOUZA, RICARDO LUIZ. Inhibition of the left medial prefrontal cortex (mPFC) prolongs the social defeat-induced anxiogenesis in mice: Attenuation by NMDA receptor blockade in the right mPFC. Behavioural Brain Research, v. 378, JAN 27 2020. (16/24568-4, 17/25409-0, 13/01283-6)

DA COSTA, VINICIUS FRESCA; RAMIREZ, JOHANA CATERIN CAIPA; RAMIREZ, STEPHANY VIATELA; AVALO-ZULUAGA, JULIAN HUMBERTO; BAPTISTA-DE-SOUZA, DANIELA; CANTO-DE-SOUZA, LUCAS; PLANETA, CLEOPATRA S.; RODRIGUEZ, JAVIER LEONARDO RICO; NUNES-DE-SOUZA, RICARDO LUIZ. Emotional- and cognitive-like responses induced by social defeat stress in male mice are modulated by the BNST, amygdala, and hippocampus. FRONTIERS IN INTEGRATIVE NEUROSCIENCE, v. 17, p. 17-pg., 2023-06-12. (16/08665-0, 17/25409-0)