Neural mechanisms of probability estimation during decision-making

项目摘要 估计不同结果的概率的能力是一种对决策至关重要的认知功能- 在不确定的环境中制造。人类决策的一个普遍特征是概率扭曲： 人类倾向于高估小概率，而低估大概率。例如，当 个人决定是购买保险还是买彩票，这些决定受到他们有多大可能性的影响 认为结果发生的概率很低。精神障碍会扰乱决策，包括 精神分裂症和双相情感障碍。因此，对大脑如何表示的电路水平的理解 决策过程中的概率结果对人类健康具有巨大影响。 我将使用高通量的行为训练来开发研究概率的行为范式 大鼠的扭曲，使得能够应用强大的工具来监测和操纵神经电路(目标1，K99 阶段)。我最近开发了一个系统，可以对大量的人进行细胞分辨率成像 自愿性头部束缚时大鼠认知行为的神经元。我将使用这个系统，结合使用 用新开发的表达钙指示剂GCaMP6f的转基因大鼠，记录从100s到1000s的 大脑皮层神经元的行为估计概率(目标2，K99阶段)。我将开发和应用解码 明确测试有关神经群体如何表示概率的假设的方法。结合了 成像数据和解码方法，我将确定大脑皮层处理阶段的概率 失真出现(目标2，K99阶段)。最后，我将进行光遗传和药物微扰 描述概率失真背后的功能因果电路的实验(目标3，R00阶段)。我 然后将光遗传学和相互连接的大脑区域的双光子成像结合起来，以评估 概率的表示跨越多个大脑区域传播，并由多个大脑区域表示。加在一起，这些 实验将建立大鼠作为研究概率的经济有效、易驯服的哺乳动物模型。 失真，并将产生相关电路和机制的信息丰富的工作模型 动物计算、表示和扭曲概率的估计。 大鼠自愿头部约束成像系统是作为 Tank和Brody实验室之间的合作，使普林斯顿成为我学习这些知识的唯一地方 技巧。此外，普林斯顿神经科学研究所强大的协作环境使 这是我追求这些研究目标的理想场所。我的培训计划提供了详细的战略 在K99阶段从具有广泛的、经过验证的专业知识的合作导师团队那里获得必要的技能 相关技术。技术培训，以及频繁的数据演示、专业人员出席 课程、研讨会和会议，以及我写作和领导技能的发展，将使我能够 过渡到一个独立的位置。在独立的R00阶段，我将使用这些获得的技能来 完成建议的目标，并建立一个专注于概率扭曲和决策研究的实验室- 使用创新的行为、成像、计算和光遗传学方法进行制作。

Project Summary The ability to estimate the probabilities of different outcomes is a cognitive function critical for decision- making in uncertain environments. A pervasive feature of human decision-making is probability distortion: humans tend to overweight small probabilities and underweight large probabilities. For example, when individuals decide to purchase insurance or play the lottery, these decisions are influenced by how likely they perceive low probability outcomes to be. Decision-making is disrupted in psychiatric disorders including schizophrenia and bipolar disorder. Therefore, a circuit-level understanding of how the brain represents probabilistic outcomes during decision-making has enormous consequences for human health. I will use high-throughput behavioral training to develop behavioral paradigms for studying probability distortion in rats, enabling application of powerful tools to monitor and manipulate neural circuits (Aim 1, K99 phase). I have recently developed a system that enables cellular resolution imaging of large populations of neurons in rats performing cognitive behaviors during voluntary head-restraint. I will use this system, combined with newly developed transgenic rats expressing the calcium indicator GCaMP6f, to record from 100s-1000s of cortical neurons as behaving rats estimate probabilities (Aim 2, K99 phase). I will develop and apply decoding methods to explicitly test hypotheses about how neural populations represent probabilities. Combining the imaging data and decoding methods, I will determine the stage of cortical processing at which probability distortion emerges (Aim 2, K99 phase). Finally, I will perform optogenetic and pharmacological perturbation experiments to delineate the functional causal circuits underlying probability distortion (Aim 3, R00 phase). I will then combine optogenetics and two-photon imaging of interconnected brain regions, to evaluate how representations of probability propagate across and are represented by multiple brain regions. Together, these experiments will establish the rat as a cost-effective, tractable mammalian model for studying probability distortion, and will produce well-informed working models of the relevant circuits and mechanisms by which animals compute, represent, and distort estimates of probabilities. The rat voluntary head-restraint imaging system has been exclusively developed as part of a collaboration between the Tank and Brody laboratories, making Princeton the only place for me to learn these techniques. In addition, the strong, collaborative environment at the Princeton Neuroscience Institute makes it an ideal place for me to pursue these research goals. My training plan provides a detailed strategy for acquiring the necessary skills in the K99 phase from a team of co-mentors with extensive, proven expertise in the relevant techniques. Technical training, as well as frequent data presentations, attendance of professional courses, seminars, and conferences, and development of my writing and leadership skills, will allow me to transition to an independent position. In the independent R00 phase, I will use these acquired skills to complete the proposed aims and build a laboratory focused on the study of probability distortion and decision- making using innovative behavioral, imaging, computational, and optogenetic approaches.