Role of GABAergic mechanisms in the inferior colliculus and periaqueductal gray matter on the sensorimotor gating of fear and anxiety

• Grant number: 12/03707-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2012
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Marcus Lira Brandão
• Grantee: Viviane Mitsuko Neves Saito
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Unconditioned defense reactions observed in mammals are organized by the Brain Aversive System, comprising, among other structures, the dorsal periaqueductal gray matter (dPAG) and inferior colliculus (IC). It has been proposed that the IC is part of the sensorimotor circuitry that processes aversive auditory information and the dPAG is considered the main output of defensive behaviors. Both structures are tonically regulated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This project addresses the chemical mediation of GABA / Benzodiazepines (BZD) on aversive information processing in the IC and the elaboration of fear responses by dPAG. Independent groups of animals with chemitrodes (electrodes attached to a guide cannula for drug injection) will be used to evaluate the IC and dPAG regarding the effects of local injections of muscimol (GABA-A agonist), semicarbazide (synthesis inhibitor of the enzyme GAD - glutamic acid decarboxylase), midazolam (BZD agonist) and flumazenil (BZD antagonist). Auditory evoked potentials will be recorded in the IC as a measure of electrophysiological neuronal activation, in addition to determining the thresholds of aversive freezing and flight, using the electrical stimulation procedure in both the IC and the dPAG. The same pharmacological regimen of drug injections intra-dPAG and intra-CI will be applied to animals subjected to the elevated plus maze (EPM), an animal model of anxiety. This project aims to expand the current knowledge on the neurobiology of fear and anxiety, in an integrative approach of the processing mechanisms of sensory input and expression of defensive behaviors.

Scientific publications

(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)

SAITO, VIVIANE M.; BRANDAO, MARCUS L.. The benzodiazepine midazolam acts on the expression of the defensive behavior, but not on the processing of aversive information, produced by exposure to the elevated plus maze and electrical stimulations applied to the inferior colliculus of rats. Neuropharmacology, v. 88, n. SI, p. 180-186, JAN 2015. (12/03707-5, 11/00041-3)

SAITO, VIVIANE M.; BRANDAO, MARCUS L.. THE LIGHT SWITCH-OFF RESPONSE AS A PUTATIVE RODENT TEST OF INNATE FEAR. Neuroscience, v. 334, p. 160-165, OCT 15 2016. (12/03707-5)

SAITO, VIVIANE M.; BRANDAO, MARCUS L.. The benzodiazepine midazolam acts on the expression of the defensive behavior, but not on the processing of aversive information, produced by exposure to the elevated plus maze and electrical stimulations applied to the inferior colliculus of rats. Neuropharmacology, v. 88, p. 7-pg., 2015-01-01. (12/03707-5, 11/00041-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SAITO, Viviane Mitsuko Neves. Role of GABAergic mechanisms in the inferior colliculus and periaqueductal gray matter on the sensorimotor gating of fear and anxiety. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC) Ribeirão Preto.