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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

Grant number: 20/15050-7
Support type:Regular Research Grants
Duration: June 01, 2022 - May 31, 2024
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal researcher:Norberto Cysne Coimbra
Grantee:Norberto Cysne Coimbra
Home Institution: Instituto de Neurociências e Comportamento (INEC). Ribeirão Preto , SP, Brazil
Assoc. researchers:Rafael Carvalho Almada

Abstract

There is a great scientific interest in the search of the neuropsychopharmacological bases of fear- and panic-like behaviour. Several studies suggest the mesencephalic tectum (MT) as responsible for the control of defensive responses elaborated during threatening situations. The deep layers of the superior colliculus (dlSC) are considered relevant structures for the elaboration of innate fear and defensive behaviour. The substantia nigra, pars reticulata (SNpr), is known for its role in the modulation of the activity of the intermediate layers of the superior colliculus (ilSC) and dlSC and can work as a sensorial channel to tectal neurons responsible for the organization of defensive reactions in cranial mesencephalon. There is evidence that the neocortex send connexions to the neostriatum, which through globus pallidus is connected to the SNpr. The reticulate division of the substantia nigra in turn sends GABAergic connexions to the tectum. Outputs from ventromedial division of the SNpr are also connected to the CPu. The basal nuclei, particularly the globus pallidus and functionally related structures, such the SNpr, have elevated density of cannabinoid receptors type 1 (CB1) and TRPV1. In the globus pallidus, these receptors are situated presinapticaly, mainly in GABaergic neurons connected to the striatum. The present work aims to investigate the endogenous signaling of AEA and 2-AG, via CB1 and TRPV1 receptors of the globus pallidus during the organization of panic-like behaviour of rodents confronted with snakes of Bothrops genus, such as Bothrops jararaca, Bothrops alternatus e Bothrops moojeni. In addition, the morphology of the nigro-tectal pathway will be also studied, focusing on the GABAergic neurons subtype connected to the dlSC. For that purpose, it will be studied the effect of microinjections of AM251, a CB1- receptor antagonist, URB597, a FAAH inhibitor, URB602, a 2-AG hydrolysis inhibitor, and the TRPV1 antagonist 6-hidroxi-capsaicin, in the globus pallidus, on the elaboration of the defensive behaviour by dorsal midbrain structures induced by dlSC GABAA receptor blockade in rats threatened by wild snakes. Finally, in a neuroanatomical approach, it will be investigated the morphologic characteristics of the GABAergic neurons connected to the dlSC. (AU)

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