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

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.