Prefrontal-subcortical circuitry underlying cognitive flexibility

灵活利用信息并根据变化的环境条件执行适当行为的能力对所有物种的生存都至关重要。在某些情况下，灵活的行为能够更有效地追求奖励（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。我们小组的工作表明，认知灵活性的不同组成部分依赖于额叶和各种皮层下系统之间的功能相互作用。然而，在这些类型的执行功能的调解中，这些回路之间相互作用的细胞和神经化学机制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中特定事件相关的神经活动（例如，在行动选择之前或在行动结果之后）是如何促进行为变化的。此外，我们对大脑回路和神经化学的理解是有限的灵活反应在负面动机的情况下。考虑到这些问题，本研究计划有两个主要目标；1)利用时间精确光遗传沉默，探索额叶和腹侧纹状体不同区域策略转移和概率逆转学习的神经基础以及这些系统之间的相互作用。2)绘制出与多巴胺系统相关的神经回路，该系统促进了不同形式的厌恶动机行为，使用在探索其他形式的灵活性方面已被证明富有成效的传统方法。这些行为包括那些需要区分与厌恶与中性结果和厌恶条件反射相关的刺激的行为，以及那些需要生物体灵活调节做出或保留反应以避免惩罚的行为。通过结合光遗传学和传统行为药理学方法的电路分析方法，本研究将提供有价值的见解，了解前额叶-纹状体电路中不同节点相互作用以调节食欲和厌恶动机行为的策略选择和认知灵活性的机制。因此，这条研究路线最终将导致对分布式神经网络如何调节促进生存的行为适应的更好理解。

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.