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: 10582133
• 负责人: Stephanie Mary Groman
• 金额: $ 68.55万
• 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 2027-07-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582133
• 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; 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; Synapses; System; Techniques; Testing; Update; Ventral Tegmental Area; Viral; Virus; age related; awake; base; cingulate cortex; critical period; imaging study; improved; in vivo; in vivo calcium imaging; in vivo optical imaging; innovation; insight; neural circuit; neural network; neurodevelopment; optogenetics; ranpirnase; relating to nervous system; translational study

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 青春期是神经发育的最关键时期之一。大脑经历了深刻的 在此阶段重组，包括控制决策的神经回路的形成和稳定 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 在编码特定决策机制的大脑电路中。支持这一假设的直接证据， 但是，有限。尤其是前额叶皮层在 青春期和大脑成像研究已经观察到轨道额皮层（OFC）和 前扣带回皮质（ACC）。精神病患者的OFC和ACC发生了变化，这是可以认为的 是这些临床人群中出现的决策缺陷的基本机制。什么时候和 这些变化的发生方式尚不清楚，但是新出现的证据表明皮质下的发展变化 可能涉及OFC和ACC的预测。在这里，我们建议在体内钙成像中使用 光遗传技术以及计算建模，纵向评估电路和神经元 在多个青少年时代的行为大鼠的活动，以确定OFC和ACC中的发育变化如何 网络调解了决策的改进。在目标1中，我们将确定如何编码注意力和 杏仁核和腹侧段区域（VTA）预测OFC的奖励预测错误会改善 使用逆向学习任务的大鼠青春期。然后，我们将在AIM中使用一种新的透射性追踪方法 2证明杏仁核和VTA预测控制的关注和奖励预测错误是 集成到OFC神经元中，以确定更新和加强动作值的程度 在青春期。最后，AIM 3研究将研究OFC预测对ACC的作用 使用当前的行动价值估计值进行自适应决策。在一起，这些研究 将提供有关指导复杂决策的发展机制的关键见解。我们的规范 数据将为识别和理解心理的神经发育机制提供一个框架 疾病，并激发未来的翻译研究。