Prefrontal-subcortical circuitry underlying cognitive flexibility

灵活地使用信息并执行适当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必不可少的。在某些情况下，灵活的行为能够更有效地追求回报(如食物)，而在其他情况下，这些过程有助于重新组织行为，以应对潜在的厌恶后果。我们团队的研究表明，认知灵活性的不同组成部分取决于额叶和各种皮质下系统之间的功能相互作用。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些类型的执行功能方面仍然存在重要的问题。例如，目前尚不清楚这些不同区域内与学习过程的特定事件相关的神经活动(例如，在动作选择之前或动作结果之后)如何促进行为的改变。此外，我们对厌恶动机情境下灵活反应背后的大脑回路和神经化学的理解也是有限的。考虑到这些问题，本研究提案有两个主要目标； 1)利用时间上精确的光遗传沉默，探讨额叶和腹侧纹状体不同区域的策略转移和概率反转学习的神经基础，以及这些系统之间的相互作用。 2)利用已被证明在探索其他形式的灵活性方面卓有成效的传统方法，绘制出与多巴胺系统相连的神经回路，该回路促进了不同形式的厌恶动机行为。这些行为包括那些需要区分与厌恶和中性结果和厌恶条件有关的刺激，以及那些要求有机体灵活地调节做出或抑制反应以避免惩罚的行为。 通过结合光遗传和传统行为药理学方法的电路分析方法，本研究将为前额叶-纹状体回路中的不同节点相互作用以调节策略选择和认知灵活性的机制提供有价值的见解，包括食欲和厌恶动机行为。因此，这一系列研究最终将使人们更好地理解分布式神经网络如何调节促进生存的行为的适应。

The ability to use information flexibly and execute appropriate behaviours in response to changing environmental conditions is essential for survival in all species. In some instances, flexible behaviours enable more efficient pursuits of rewards (such as food), whereas in other situations, these processes aid in reorganizing behavior to deal with potential aversive consequences. Work by our group has shown that different components of cognitive flexibility are dependent on functional interactions between the frontal lobes and a variety of subcortical systems. However, important questions remain regarding the cellular and neurochemical mechanisms that underlie the interplay between these circuits in the mediation of these types of executive functioning. For example, it is currently unknown how neural activity within these different regions that is associated with specific events of the learning process (eg; before action selection or after action outcomes) serves to facilitate changes in behavior. In addition, our understanding of the brain circuitry and neurochemistry underlying flexible responding in aversively-motivated situations is limited. With these issues in mind, the present research proposal has two main objectives; 1) Explore the neural basis underlying strategy shifting and probabilistic reversal learning in different regions of the frontal lobes and ventral striatum and the interactions between these systems, using temporally-precise optogenetic silencing. 2) Map out the neural circuitry linked with the dopamine system that facilitates different forms of aversively-motivated behaviors, using traditional approaches that have proven fruitful in exploring other forms of flexibility. These behaviors include those requiring discrimination between stimuli linked to aversive vs neutral outcomes and aversive conditioning, and those requiring an organism to flexibly regulate making or withholding responses to avoid punishments. By utilizing a circuitry analysis approach combined with optogenetic and traditional behavioural pharmacological methods, this research will provide valuable insight into the mechanisms by which different nodes within the prefrontal-striatal circuitry interact to regulate strategy selection and cognitive flexibility for both appetitive and aversively-motivated behaviors. As such, this line of research ultimately will lead to a greater understanding of how distributed neural networks regulate adaptations of behaviour that promote survival.