The anterior cingulate cortex and its interface with the dorsal periaqueductal grey regulating nitric oxide-mediated panic-like behaviour and defensive antinociception

Author(s)

Falconi-Sobrinho, Luiz Luciano ; dos Anjos-Garcia, Tayllon ; Rebelo, Macario Arosti ; Hernandes, Paloma Molina ; Almada, Rafael Carvalho ; Tanus-Santos, Jose Eduardo ; Coimbra, Norberto Cysne

• Document type: Journal article
• Source: Neuropharmacology; v. 245, p. 17-pg., 2024-01-01.

Abstract

The anterior cingulate cortex (ACC) Cg1 (24b) area modulates glutamate -mediated unconditioned fear and antinociception organised by hypothalamus. However, it remains unknown whether 24b area also modulates these latter defensive responses through connections with the dorsal periaqueductal grey matter (dPAG), a midbrain structure implicated in the genesis of innate fear -induced defence. The aim of this work is to examine the correlation between the behavioural effects of intra-ACC microinjections of vehicle, NMDA (1 nmol) or lidocaine (2%) with Fos protein expression and nitrergic activity in the dPAG of male C57BL/6 mice that were threatened by snakes. In addition, the 24b area-dPAG pathways were also characterised by neural tract tracing procedures. Finally, the effect of dPAG pretreatment with the neuronal nitric oxide synthase inhibitor N(omega)propyl-L-arginine (NPLA; 0.2, 0.4 or 0.8 nmol) 10 min before 24b area treatment with NMDA on behavioural and nociceptive responses of threatened mice was studied. The activation of 24b area N-methyl-D-aspartic acid receptors facilitated escape and freezing rather than risk assessment, and enhanced Fos expression and nitrite levels in dPAG, while lidocaine decreased escape and risk assessment as well as Fos and nitrergic activity in dPAG. In addition, dPAG pretreatment with NPLA suppressed intra-24b NMDA-facilitated panicogenic effects while increased nociception. Infusions of an antegrade neurotracer into 24b area showed axonal fibres surrounding both dorsomedial and dorsolateral PAG perikarya. Neurons were identified in 24b area after deposits of a retrograde neurotracer into dPAG. Our findings suggest that the ACC/24b area modulates innate defensive responses through the recruitment of dPAG nitrergic neurons. (AU)

• FAPESP's process: 17/11855-8 - Study of corpus striatum and ventral mesencephalon endocanabinoid influence on neostriato-nigro-tectal GABAergic pathways during panic reactions of rodents threatened by venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/05255-3 - Study of the role of glutamatergic pathways from the anterior cingulate cortex on nitrergic mechanisms of the ventromedial hypothalamus and periaqueductal grey matter involved in the genesis of defensive responses evoked in mice threatened by snakes
• Grantee: Luiz Luciano Falconi Sobrinho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/22647-7 - Study of glutamatergic pathways from the medial amygdala on ventromedial hypothalamus endocannabinoid signalling during the defensive behaviour elicited by mice threatened by venomous snakes
• Grantee: Tayllon dos Anjos Garcia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/15050-7 - Study of the role played by endocannabinoid and endovaniloid signalling in the pallidum on the activity of the neostriatum-pallido-nigral disinhibitory and nigro-tectal inhibitory pathways during the organization of innate fear of animals confronted to snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/14073-6 - Testing emotional vulnerability to threat in adults using a virtual reality paradigm of fear associated with autonomic variables
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/22681-7 - Involvement of Opioid and Endocanabinoid Receptors of the Substantia Nigra, Pars Reticulata, in the Modulation of the Activity of Nigro-Tectal GABAergic Pathways during the Organization of Defensive Behaviour of Mice Confronted with Venomous Snakes
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/03898-1 - Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/01713-7 - Fear and anxiety: role of orexinergic system in the prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/10984-8 - Influence of the anterior cingulate cortex and involvement of hypothalamic NMDA and AMPA/kainite glutamatergic receptorsin the organization of the defensive behaviorand innate fear-induced antinociception elaborated by posterior hypothalamus
• Grantee: Luiz Luciano Falconi Sobrinho
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants