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Neuroanatomical and psychopharmacological study of the striated-nigro-tectal GABAergic link, intramesencephalic connections and the influence of these pathways on the defense behavior elicited by stimulation of the inferior colliculus

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Author(s):
Lissandra Castellan Baldan
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Norberto Cysne Coimbra; Norberto Garcia Cairasco; Francisco Silveira Guimarães
Advisor: Norberto Cysne Coimbra
Abstract

The electrical and chemical stimulation of some midbrain structures, such as the dorsal periaqueductal gray matter (DPAG), deep layers of the superior colliculus and central e pericentral nucleus of the interior colliculus, elicit defensive behavior, similar to these feel-like reactions described in panic disorder. The substantia nigra, a midbrain structure rich in GABAergic neurons, also receives GABAergics inputs from the striatum and sends inputs to the dorsal mesencephalon, more rostrally, modulating the neural substrate of fear in the superior colliculus and DPAG. The aim of this work consist in studying if these GABAergic connections reach also modulatory targets in the aversive substrate of the inferior colliculus, effecting aversive responses elicited by electrical stimulation of the caudal midbrain tectum. The neuroanatomy of the connections between the central nucleus of the inferior colliculus and the dorsal columns of the periaqueductal gray matter was also investigated. The nigrotectal pathway was labeled with retrograde fluorescent neurotracer fast blue, microinjected in the central nucleus of the inferior colliculus and with the non-fluorescent neurotracer biodextran, iontophoretically microinjected in the substantia nigra, pars reticulata (SNpr). The effects of the decrease of the activity of this pathway were studied, through electrolytic and neurochemical lesions (with ibotenic acid) of the substantia nigra, pars reticulata. The retrograde neurotracer showed neuronal cells located in the substantia nigra, pars reticulata, both ipsi- and contralaterally. This nigro-tectal pathway was corroborated by the anterograde neurotracer (BDA), that showed axonal fibers in the central nucleus of the inferior colliculus. Both the electrolytic and the neurochemical lesions of the SNpr decreased the aversive thresholds elicited by electrical stimulation of the interior colliculus. Intramesencephalic connections were studied by means of iontophoretical microinjections of biodextran in the central nucleus of the inferior colliculus, allowing the identification of pathway with axons rich in varicosities connecting the central nucleus of the inferior colliculus to caudal dorsomedial and lateral columns of the periaqueductal gray matter, where fear-induced behavior may be organized. The GABA-A receptors blockade in the central nucleus of the inferior colliculus was followed by vigorous defensive responses, characterized by freezing, following by running, jumping and rotations, suggesting a tonic inhibitory role of GABAergic pathways on the neural substrate responsible by elaboration of fear-like responses in the inferior colliculus, central nucleus. (AU)