Circuit-level neurodevelopmental trajectories of decision-making computations across adolescence

青春期决策计算的电路级神经发育轨迹

• 批准号: 10705252
• 负责人: Stephanie Mary Groman
• 金额: $ 71.41万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705252
• 关键词: Adolescence; Adolescent; Adult; Age; Amygdaloid structure; Anterior; Attention; Behavior; Brain; Brain imaging; Brain region; Calcium; Clinical; Complex; Computer Models; Coupled; Data; Decision Making; Development; Dimensions; Fiber; Future; Image; Individual; Learning; Link; Mediating; Mental disorders; Methods; Midbrain structure; Neurons; Outcome; Photometry; Population; Prefrontal Cortex; Process; Proto-Oncogene Proteins c-abl; Psychological reinforcement; Rattus; Reporting; Reversal Learning; Rewards; Role; ST5 gene; Signal Transduction; Site; Synapses; System; Techniques; Testing; Update; Ventral Tegmental Area; Viral; Virus; age related; awake; cingulate cortex; computational reasoning; critical period; imaging study; improved; in vivo; in vivo calcium imaging; in vivo optical imaging; innovation; insight; neural; neural circuit; neural network; neurodevelopment; optogenetics; postnatal; translational study; transmission process

Project Summary Adolescence is one of the most critical periods of neurodevelopment. The brain undergoes a profound reorganization during this stage, including the formation and stabilization of neural circuits that control decision- making. We, and others, hypothesize that age-related improvements in decision-making are driven by changes in brain circuits that encode specific decision-making mechanisms. Direct evidence supporting this hypothesis, however, has been limited. The prefrontal cortex in particular undergoes an intense restructuring during adolescence and brain imaging studies have observed robust changes in the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC). The OFC and ACC are altered in individuals with mental illness, which is thought to be the mechanism underlying decision-making deficits that emerge in these clinical populations. When and how these alterations occur is not known, but emerging evidence suggests developmental changes in subcortical projections to the OFC and ACC may be involved. Here, we propose to use in vivo calcium imaging and optogenetic techniques coupled with computational modeling, to longitudinally assess circuit and neuronal activity in behaving rats at multiple adolescent ages to determine how developmental changes in OFC and ACC networks mediate improvements in decision-making. In Aim 1 we will determine how encoding of attention and reward-prediction errors in amygdala and ventral tegmental area (VTA) projections to the OFC improves across adolescence in rats using a reversal-learning task. We will then use a new transsynaptic tracing approach in Aim 2 to demonstrate that attention and reward prediction errors controlled by amygdala and VTA projections are integrated into OFC neurons to determine the degree to which action values are updated and strengthened during adolescence. Finally, Aim 3 studies will investigate the role of OFC projections to the ACC in integrating value updating with current action value estimates that guide adaptive decision making. Together, these studies will provide key insights into the developmental mechanisms that guide complex decision making. Our normative data will provide a framework for identifying and understanding the neurodevelopmental mechanisms of mental illness, and inspire future translational studies.

项目摘要 青春期是神经发育最关键的时期之一。大脑经历了一个深刻的 重组在这个阶段，包括形成和稳定的神经回路，控制决策- 制作。我们和其他人假设，与年龄相关的决策改善是由变化驱动的 在大脑回路中编码特定的决策机制。支持这一假设的直接证据， 然而，这是有限的。特别是前额皮质在经历了一次剧烈的重组后， 青春期和脑成像研究已经观察到眶额皮质（OFC）的强烈变化， 前扣带皮层（ACC）。OFC和ACC在精神疾病患者中发生改变， 是这些临床人群中出现的决策缺陷的潜在机制。何时以及 这些变化是如何发生的尚不清楚，但新出现的证据表明，皮层下的发育变化， 可能涉及对OFC和ACC的预测。在这里，我们建议使用体内钙成像， 光遗传学技术与计算建模相结合，纵向评估回路和神经元 在多个青春期年龄的行为大鼠中的活动，以确定OFC和ACC的发育变化 网络有助于改善决策。在目标1中，我们将确定如何编码的注意力和 杏仁核和腹侧被盖区（VTA）对眶额皮层的投射中的奖赏预测错误在整个研究中得到改善。 青春期大鼠使用反向学习任务。然后，我们将在Aim中使用一种新的跨突触追踪方法 2证明杏仁核和腹侧被盖区投射控制的注意力和奖励预测错误是 整合到OFC神经元中，以确定动作值更新和加强的程度 在青春期。最后，目标3研究将调查OFC投射到ACC在整合中的作用。 用当前动作值估计进行值更新，以指导自适应决策。这些研究一起 将为指导复杂决策的发展机制提供关键见解。我们的规范 数据将提供一个框架，用于识别和理解精神疾病的神经发育机制。 疾病，并启发未来的转化研究。