Thalamic regulation of prefrontal dynamics in decision making under uncertainty

丘脑对不确定性决策中前额叶动态的调节

• 批准号: 10773415
• 负责人: Arghya Mukherjee
• 金额: $ 10.92万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10773415
• 关键词: Animal Behavior; Animals; Attention; Auditory; Behavior; Behavioral; Belief; Belief System; Biological Models; Brain; Communication; Communities; Complex; Conflict (Psychology); Cues; Data; Decision Making; Dedications; Development Plans; Dissection; Dorsal; Economics; Electrophysiology (science); Environment; Failure; Foundations; Future; Genetic; Human; Learning; Maps; Mental disorders; Mentors; Modeling; Modernization; Molecular; Mus; Neurons; Noise; Outcome; Phase; Population; Prefrontal Cortex; Primates; Probability; Process; Psychiatry; Psychological reinforcement; Psychoses; Psychotic Disorders; Regulation; Research; Research Proposals; Rewards; Rodent; Role; Schizophrenia; Sensory; Signal Transduction; Source; Specific qualifier value; Stimulus; Structure; System; Techniques; Testing; Thalamic structure; Therapeutic; Training; Tupaia; Tupaiidae; Uncertainty; Update; Visual; attentional control; behavioral outcome; career; career development; cell type; cognitive control; cognitive neuroscience; cognitive process; experimental study; frontal lobe; in vivo; neural; neural circuit; optogenetics; public health relevance; sensory input; statistics; targeted treatment; tool; translational study

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.

抽象的： 研究计划：决策是根据感官提示或选择行动的过程 期望结果的价值。对于他们的功能决策系统至关重要，例如前额皮质（PFC）， 需要捕捉其环境的因果结构（内部模型或信念系统）并更新其 当潜在关联发生变化时的内部信念。 虽然人们在理解 PFC 内的神经回路机制方面付出了很多努力，但最近的发现 表明与内侧背侧丘脑（MD）的相互作用对其功能至关重要，尤其是 当必须使用嘈杂的信息做出决策时，这一点很重要。此外，未能解决噪音问题 更新内在信念被认为是精神分裂症和相关精神病的基础。因此， 确定 MD-PFC 相互作用的回路机制不仅与认知神经科学相关，而且与 也涉及精神病学。该 K99/R00 研究提案将探讨 MD 在调节 PFC 动态方面的作用 通过以下三个目标在不确定的情况下进行决策。目标 1，将探索基因是否 MD 内的可识别人群，由于其与 PFC 的独特连接，被选择性地调整 解决由高噪声与低信号引起的感觉输入不确定性。目标 2 将探索 MD 在使用树鼩（Tupaia）研究类人推理的多步决策范式中的作用， 类似于基础灵长类动物。前两个Aims 2将在K99训练阶段进行。在目标 3 中， 在独立 R00 阶段执行的目标 1 和 2 的发现将扩展到经济决策 在预期回报水平存在不确定性的情况下进行决策。这些目标共同将阐明 MD-PFC 相互作用在解决决策不确定性方面发挥作用的电路机制 并将进一步提供精确的目标，通过这些目标可以治疗决策缺陷 有所改善。 职业发展计划：K99 培训将提供学习该活动所需的工具和培训 大脑中的神经元来破译潜在的电路机制。 R00阶段将奠定基础 由实验驱动的独立研究生涯，将复杂的决策解构为 由指定电路提供服务的更简单的认知过程的组合。

项目成果

The Associative Thalamus: A Switchboard for Cortical Operations and a Promising Target for Schizophrenia.

联想丘脑：皮层操作的总机和精神分裂症的有希望的目标。

• DOI: 10.1177/10738584221112861
• 发表时间: 2022-08-08
• 期刊: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
• 作者: Arghya Mukherjee;Michael M. Halassa
• 通讯作者: Michael M. Halassa