Cortico-thalamic-striatal circuitry and cognitive flexibility

灵活利用信息和执行适当的适应性行为以应对不断变化的环境条件的能力对所有物种的生存都至关重要。前额叶皮层（PFC）是促进认知灵活性的一个关键区域，它通过抑制先前策略的执行来允许新行为的出现。然而，重要的问题仍然是关于细胞和神经化学机制，这些机制是这些回路之间相互作用的基础，在这种类型的执行功能的调解中。这项研究旨在进一步阐明啮齿动物的大脑如何利用多学科方法解决这些问题。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）如何在腹侧纹状体中起作用，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节行为以适应环境变化中所起的作用。在另一个目标中，我们将记录醒着的、有行为的动物在执行任务时的神经活动，这些任务需要它们以灵活的方式行事。这将使我们能够识别特定的代码，这些代码是PFC等区域的神经元用来发出信号，表明环境已经改变，动物的行为必须随之改变。本研究将为PFC和相关皮层下核相互作用调控策略选择和认知灵活性的机制提供有价值的见解。这些研究最终将有助于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，鉴于许多精神障碍都与认知灵活性受损有关，这些研究的结果可能会对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.