Corticostriatal contributions to evidence evaluation and decision selection

项目摘要 认知灵活性的一个决定性特征是能够对信息如何进行控制 在采取行动时受到的待遇。这对决策很重要，决策通常涉及 评估来自周围环境的信息以选择合适的选择。皮质纹状体 电路被认为在这些决策过程中起着关键作用，但它们确切的 捐款仍未解决。我们的长期目标是了解皮质纹状体回路是如何 有助于灵活控制证据评估和决策选择。关于啮齿动物的研究 已确定大脑皮质和前背侧纹状体中的额叶定向场(FOF) (ADS)，它预计在证据评估和决定中发挥重要作用 选择。然而，关于这一回路如何控制证据的时间尺度，人们知之甚少。 指导决策选择的评估，这对于证据存在的任何情况都很重要 在时间上连续获得的。在之前工作的基础上，我们的总体假设是 广告在控制证据对选择的影响期间起着作用，而FOF 在通过广告传递的信息指导下的决策选择中发挥作用。在这里，我们训练 执行我们为解决这些问题而开发的一种新的变化检测任务 问题。在目标1中，我们将确定广告的贡献，以控制 证据评估。我们将使用神经记录和光遗传学的组合 微扰来研究神经表示和相关的电路机制。在目标2中，我们 将通过并行方法确定FOF对自由响应决策选择的贡献 作为目标1，再次将神经记录和光遗传扰动结合在一起。在《目标3》中，我们将 用同步神经记录测量ADS和FOF对彼此的影响 告知皮质纹状体回路的机制模型对证据评估和 决策选择。我们采取的方法是创新的，因为实验室开发出了新的 技术，前沿技术的重要改进，以及已建立的 以前未探索过的问题的技巧。这项工作的贡献是巨大的 因为它将填补我们关于这一至关重要的功能的知识的多个主要空白 和临床相关的回路。此外，由于皮质纹状体回路和功能 在这里研究的人受到多发性大脑疾病的影响，加深了对 两者之间的联系将有助于开发新的精神健康治疗方法和 避免针对这些大脑回路的治疗的副作用。

Project Summary A defining feature of cognitive flexibility is the ability to exert control over how information is treated when acting upon it. This is important for decision making, which often involves evaluating information from one's surroundings to select appropriate choices. Corticostriatal circuits have been suggested to play critical roles in these decision processes, but their exact contributions remain unresolved. Our long-term goal is to understand how corticostriatal circuits contribute to flexible control of evidence evaluation and decision selection. Studies in rodents have identified the frontal orienting field (FOF) in the cortex and the anterior dorsal striatum (ADS) to which it projects as playing important roles in evidence evaluation and decision selection. However, little is known about how this circuit controls the timescale of evidence evaluation that guides decision selection, which is important for any situation where evidence is acquired sequentially in time. Building on previous work, our overarching hypothesis is that the ADS plays a role in controlling the period of influence of evidence on choices and that the FOF plays a role in decision selection that is guided by information routed via the ADS. Here, we train rats to perform a novel change detection task that we have developed to address these questions. In Aim 1, we will identify contributions of the ADS to control the timescales of evidence evaluation. We will use a combination of neural recordings and optogenetic perturbation to study neural representations and associated circuit mechanisms. In Aim 2, we will identify contributions of the FOF to free response decision selection with a parallel approach as Aim 1, again combining neural recordings and optogenetic perturbations. In Aim 3, we will measure the influence of the ADS and FOF on each other with simultaneous neural recordings to inform mechanistic models of corticostriatal circuit contributions to evidence evaluation and decision selection. The approach we take is innovative because the lab has developed novel techniques, important refinements of cutting edge techniques, and extensions of established techniques to previously unexplored questions. The contribution of this work is significant because it will fill multiple major gaps in our knowledge about this critically important function and clinically relevant circuit. Furthermore, because corticostriatal circuits and the functions studied here are impacted by multiple brain disorders, an improved understanding of the connection between the two will be useful for developing new mental health treatments and avoiding side effects of treatments targeted to these brain circuits.