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To attack or to defend? Resolution os response competition by the basal ganglia

Grant number: 14/08214-2
Support type:Regular Research Grants
Duration: July 01, 2015 - June 30, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Eliane Comoli
Grantee:Eliane Comoli
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The BG are vitally important component of the vertebrate brain that has changed little over the course of ~400 million years of brain evolution. In humans the BG are associated with numerous neurological and psychiatric conditions including Parkinson's disease, Huntington's disease, schizophrenia, attention deficit hyperactivity disorder, Tourette's syndrome, obsessive-compulsive disorder and numerous addictions. Many of these clinical conditions can be interpreted in terms of 'selection-failures' - Parkinson's disease, an inability to select any behavioural option; schizophrenia and attention deficit hyperactivity disorder, an inability to suppress the selection of competing options; obsessive-compulsive disorder and the addictions, an inability to prevent the selection of a dominant option. To appreciate the different ways a highly complex system like the BG can fail, it can only help to have a better understanding of their normal function. The research proposed in this application is designed to test an increasingly acknowledged view that considers the BG's systems level macro-architecture as a generic selection mechanism. To test the selection hypothesis we have chosen to exploit the spatial separation of two exclusive behavioural systems in different regions of rat superior colliculus (SC) that contribute to separate sub-cortical loops through the BG. The novel aspect of our approach is to study how these two anatomically identified loops operate when animals are making decisions between exclusive and conflicting responses (like defense and predation). We will use an anatomically based neural activity marker (in SC, thalamus and striatum) and retrograde tracer to examine interactions between the competing functional loops when the food deprived- rat is exposed to both predador and prey simultaneously. We will investigate the neurotransmission modulation (GABAA agonist) at strategic locations of the competing loops to suppress or boost the activity of one of the competitors and the animal's decision should be biased away from or towards that competitor's response. This study will provide important insights into how this ancient and vital part of the brain contributes to making decisions between two conflicting response systems that are critical for survival. The proposed project of research to investigate competition between sub-cortical loops through the basal ganglia (BG) is both timely and novel. (AU)