Cortico-thalamic-striatal circuitry and cognitive flexibility

灵活使用信息和执行适当的适应行为以应对不断变化的环境条件的能力，对于所有物种的生存至关重要。前额叶皮层（PFC）是通过抑制先前策略的执行来促进认知灵活性的关键区域之一，以允许新行为的出现。 然而，重要的问题仍然是关于细胞和神经化学机制，这些电路之间的相互作用，在这种类型的执行功能的调解。 这项研究旨在进一步阐明大脑如何使用多学科方法解决啮齿动物的这些问题。 我们将研究多巴胺，一种对运动，奖励和认知很重要的大脑化学物质，如何在腹侧纹状体区域起作用，以促进行为的变化。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，我们将记录清醒的、有行为的动物在执行要求它们以灵活的方式表现的任务时的神经活动。 这将使我们能够确定特定的代码，神经元的区域，如PFC使用的信号，环境已经改变，动物的行为必须改变it.The目前的研究建议将提供有价值的洞察机制，PFC和相关的皮层下核相互作用，以调节策略选择和认知灵活性。 这些研究最终将导致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.