Thalamic regulation of prefrontal dynamics in decision making under uncertainty

摘要： 研究计划：决策是一个基于感官提示或选择行动的过程 预期结果的价值。对他们的功能决策系统至关重要，比如前额叶皮质(PFC)， 需要捕获其环境的因果结构(内部模型或信念系统)并更新其 当潜在的联系改变时，内在的信念。 虽然在理解PFC内的神经回路机制方面已经做了很多努力，但最近的发现 提示与丘脑内侧背侧核(MD)的相互作用对其功能至关重要，尤其是 当必须使用噪音较大的信息进行决策时，这一点很重要。此外，未能解决噪声在 更新内在信念被认为是精神分裂症和相关精神疾病的基础。因此， 确定MD-PFC相互作用的电路机制不仅与认知神经科学有关，而且与 精神病学也是如此。这项K99/R00研究提案将讨论MD在调节PFC动态中的作用 通过以下三个目标在不确定情况下进行决策。目标1，将探索是否从基因上 MD内的可识别群体，由于他们与PFC的独特连通性，被选择性地 解决由高噪声和低信号引起的感觉输入不确定性。Aim 2将探索 MD在多步骤决策范式中的作用，以研究使用树(Tupaia)进行类人推理的方法， 它们类似于基本灵长类动物。前两个目标2将在K99培训阶段进行。在《目标3》中， 在独立的R00阶段执行，目标1和2的结果将扩展到经济决策 在预期回报的水平上存在不确定性的地方。这些目标共同作用，将阐明 MD-PFC相互作用在解决决策不确定性中发挥作用的电路机制 并将进一步提供精确的目标，通过这些目标，决策中的缺陷可以通过治疗 改善了。 职业发展计划：K99培训将提供学习活动所需的工具和培训 以破译潜在的电路机制。R00阶段将建立基础 由实验驱动的独立研究生涯，这些实验将复杂的决策解构为 更简单的认知过程的组合，由特定的回路提供服务。

Abstract: Research Plan: Decision making is a process through which actions are selected based on sensory cues or value of desired outcome. Critical to their function decision making systems, like the prefrontal cortex (PFC), need to capture the causal structure of its environment (an internal model or belief system) and update its internal beliefs when underlying associations change. While a lot of effort has gone into understanding neural circuit mechanisms within the PFC recent findings suggest that interactions with the medio dorsal thalamus (MD) is crucial for its function and are especially important when decisions must be made using information that is noisy. Moreover, failure to resolve noise in updating internal beliefs is thought to underlie schizophrenia and related psychotic illnesses. Thus, determining the circuit mechanisms of MD-PFC interactions is relevant to not only cognitive neuroscience but also to psychiatry. This K99/R00 research proposal will address the role of MD in regulating PFC dynamics during decision making under uncertainty through the following three Aims. Aim 1, will explore if genetically identifiable populations within the MD, due to their unique connectivity with the PFC, are selectively geared towards resolving sensory input uncertainty arising from high noise versus low signal. Aim 2 will explore the role of MD in a multi-step decision making paradigm to study human-like reasoning using treeshrews (Tupaia), which are akin to basal primates. The first two Aims 2 will be carried out in the K99 training phase. In Aim 3, performed in the independent R00 phase the findings from Aim 1 and 2 will be extended to economic decision making where uncertainty exists at the level of expected rewards. These Aims collectively, will elucidate the circuit mechanisms through which the MD-PFC interactions play a role in resolving uncertainty in decisions and will further provide precise targets through which deficits in decision making can be therapeutically ameliorated. Career Development Plan: The K99 training will provide the tools and training necessary to study the activity of neurons in the brain to decipher underlying circuit mechanisms. The R00 phase will build the foundations of an independent research career driven by experiments that deconstructs complex decision making into a combination of simpler cognitive processes sub served by specified circuitry.