Dopaminergic circuitry underlying cognitive flexibility

点击翻译按钮获取中文摘要

The ability to use information flexibly and execute appropriate adaptive behaviours in response to changing environmental conditions is essential for survival in all species. Our previous work has revealed the neurochemical dopamine, a key component of the brain's reward circuitry, plays a crucial role in facilitating different forms of cognitive flexibility when reward contingencies change. Yet, important questions remain regarding the precise manner in which dopamine may regulate these functions, as well as how neural activity in brain regions that receive dopamine input process information to facilitate alterations in behaviour. The present proposal will explore how different nodes in the brain reward circuitry contribute to cognitive flexibility using rats as a model system. Over three primary aims, we will; 1) clarify how brief, "phasic" increases and decreases in dopamine activity that signal rewarded and non-rewarded events facilitate shifts between different strategies, using pharmacological and brain stimulation techniques, 2) clarify how neurons in the ventral striatum (a key dopamine input region) change their firing patterns when an organism must adjust behaviour upon changes in well-established rules and 3) explore the neural circuits that regulate cognitive flexibility when reward delivery is uncertain/probabilistic, using a variety of brain inactivation and pharmacological approaches. This information will provide crucial insight into how the brain's reward system contributes to different aspects of reward-related learning and modification of learned behaviours. Given the similarities in the anatomical connectivity of the rodent and primate brain, these studies will have considerable impact on the direction of brain imaging and neuropsychological studies of the neural mechanisms that regulate these processes in humans. Moreover, as a number of psychiatric disorders are associated with impairments in cognitive flexibility, this basic research may yield important insight into the brain dysfunction that underlies these types of cognitive deficits. Thus, this line of research ultimately will lead to a greater understanding of how distributed neural networks in the brain deals with unexpected changes in its environment to promote survival.