Cortico-thalamic-striatal circuitry and cognitive flexibility

灵活地使用信息并执行适当的适应行为以应对环境条件变化的能力对于所有物种的生存都是至关重要的。前额叶皮质(PFC)是促进认知灵活性的关键区域之一，它通过抑制先前策略的执行来允许新行为的出现。然而，关于这些回路之间相互作用的细胞和神经化学机制在调节这种类型的执行功能方面仍然存在重要的问题。这项研究旨在利用多学科方法进一步阐明大脑是如何解决啮齿动物的这些类型的问题的。我们将研究多巴胺，一种对运动、奖励和认知至关重要的大脑化学物质，如何在被称为腹侧纹状体的区域发挥作用，以促进行为的改变。其他实验将使用新的分子技术来确定突触强度的变化在调整行为以适应环境变化方面所起的作用。在另一个目标中，我们将记录动物清醒后的神经活动，这些动物执行要求它们以灵活方式行事的任务。这将使我们能够识别PFC等区域的神经元使用的特定代码，以发出环境改变的信号，动物的行为也必须随之改变。目前的研究方案将为PFC和相关皮质下核团相互作用调节策略选择和认知灵活性的机制提供有价值的见解。这些研究最终将使人们更好地理解哺乳动物大脑中的分布式神经网络如何调节动物应对环境变化的能力，并相应地调整其行为以促进其生存。此外，鉴于许多精神障碍与认知灵活性受损有关，这些研究的结果可能为了解这些疾病背后的神经功能障碍提供重要的见解。

The ability to use information flexibly and execute appropriate adaptive behaviours in response to changing environmental conditions is essential for survival in all species. The prefrontal cortex (PFC) is one region that is critical in facilitating cognitive flexibility by inhibiting the execution of a previous strategy to permit the emergence of new behaviours. However, important questions remain regarding the cellular and neurochemical mechanisms that underlie the interplay between these circuits in the mediation of this type of executive functioning. This research is designed to further clarify how the brain solves these types of problems in rodents, using a multidisciplinary approach. We will investigate how dopamine, a brain chemical important for movement, reward and cognition, acts in a region termed the ventral striatum, to facilitate changes in behaviour. Other experiments will use novel molecular techniques to identify what role changes in the strengths of synapses play in adjusting behaviour to changes in one's environment. In another aim, we will record neural activity from awake, behaving animals performing tasks that require them to behave in a flexible manner. This will enable us to identify the specific codes that neurons in regions such as the PFC use to signal that the environment has changed and that the animal's behaviour must change with it. The present research proposal will provide valuable insight into the mechanisms by which the PFC and related subcortical nuclei interact to regulate strategy selection and cognitive flexibility. These studies will ultimately will lead to a greater understanding of how distributed neural networks in the mammalian brain regulate an animal's ability to deal with changes in its environment and adapt its behaviour accordingly to promote its survival. Furthermore, in light of the fact that a number of mental disorders are associated with impairments in cognitive flexibility, the results of these studies may offer important insight into the neural dysfunction that underlies these conditions.