Implications of Prefrontal Cortex Development for Adolescent Reward Seeking Behavior

前额皮质发育对青少年奖励寻求行为的影响

• 批准号: 10739548
• 负责人: Gabriela Manzano Nieves
• 金额: $ 11.25万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739548
• 关键词: Address; Adolescence; Adolescent; Adolescent Behavior; Adolescent Development; Adult; Advisory Committees; Age; Anatomy; Animal Model; Animals; Area; Atlases; Basic Science; Behavior; Behavioral; Biological Markers; Brain; Calcium; Cells; Code; Cognitive; Communities; Cues; Data; Data Analyses; Decision Making; Detection; Development; Discrimination; Disease; Equilibrium; Exhibits; Experimental Designs; Failure; Feedback; Fiber; Future; Genetic; Glutamates; Image; Impulsivity; Influentials; Learning; Life; Link; Longitudinal Studies; Medial; Mental disorders; Mentors; Motivation; Mus; Neurons; Neurosciences; Outcome; Peripheral; Phase; Photometry; Play; Prefrontal Cortex; Property; Regulation; Research; Rewards; Role; Sensory; Shapes; Signal Transduction; Sucrose; Task Performances; Techniques; Testing; Training; Ventral Tegmental Area; Work; age related; anatomical tracing; behavior change; career; career development; cell cortex; design; early adolescence; emotion regulation; expectation; feeding; flexibility; human model; insight; neural; neuronal circuitry; optogenetics; postnatal development; response; sensory stimulus; theories; tool; transmission process; two-photon

PROJECT SUMMARY As we get older, we learn to modulate our behaviors to optimize reward outcomes. These adaptive choices are orchestrated by current sensory conditions, internal cognitive states, and future expectations. In adolescence, rewards circuits that link peripheral detection of sensory stimuli to central circuits involved in decision-making and motivational states continue to grow, remodeling the microcircuit connectivity within the medial prefrontal cortex (mPFC). This development may explain why adolescents demonstrate increased impulsivity and diminished behavioral flexibility, and fail to optimize reward outcomes. However, the developmental changes within the reward circuits that inform differences in reward learning during adolescence are poorly understood. The mPFC is a key area for emotional regulation, decision making, and reward-seeking. The reward- modulating properties of mPFC are derived from inputs from the ventral tegmental area (VTA). During adolescence, VTA inputs into mPFC are still developing, and the functional impact of these developmental changes is unknown. One influential theory suggests that increased dopaminergic (DA) signaling in adolescence drives heightened reward sensitivity. However, additional mechanisms such as changes in local mPFC connectivity and changes in reward information sent to the mPFC are likely at play. In this proposal, we use a combination of chemogenetics, optogenetics, anatomical, and neural calcium imaging, to test how the developing adolescent mPFC (Aim 1) and VTA projections to mPFC (Aim 2) contribute to adolescent reward behaviors and influence reward optimization strategies (Aim 3). This work reframes the role of neuronal subtypes, and probes if their role in a given behavior is shaped by the age of the microcircuit, asking the question, do cells carry the same information in adolescents as they do in adulthood? In addition to the value of this work from a basic science perspective, this study is likely to produce testable hypotheses that will tackle why certain psychiatric disorders such as impulse control and feeding disorders tend to emerge during adolescence. Training in calcium imaging, neuronal activity data analysis and advanced anatomical techniques will be provided by the mentor Dr. Conor Liston, with additional expertise in 2-photon imaging provided by the consultants Drs. Rajasethupathy and De Marco Garcia. Dr. Sullivan will serve as a consultant on developmental behavioral neuroscience, providing feedback on experimental design and outcomes. Dr. Bravo Rivera will provide an additional behavioral neuroscientific perspective and will be instrumental in providing additional career development training to the applicant. Together the mentor and the External Advisory Committee will facilitate the transition of Dr. Manzano Nieves into an independent research career focused on uncovering how postnatal development alters brain circuits to bias behavior and create psychiatric vulnerabilities.

项目摘要 随着年龄的增长，我们学会调节行为以优化奖励结果。这些适应性选择是 由当前的感官条件，内部认知状态和未来的期望策划。在青春期， 将感觉刺激的外围检测与参与决策涉及的中央电路联系起来的奖励电路 动机状态继续增长，重塑内侧前额叶内的微电路连接 皮质（MPFC）。这种发展可以解释为什么青少年表现出增加的冲动性和 行为灵活性降低，无法优化奖励结果。但是，发展变化 在为青春期奖励学习差异的奖励电路中，人们对奖励学习的差异知之甚少。 MPFC是情感调节，决策和寻求奖励的关键领域。奖励 - MPFC的调节特性是从腹侧段区域（VTA）的输入得出的。期间 青春期的VTA输入MPFC仍在发展，这些发展的功能影响 变化未知。一种有影响力的理论表明，增加多巴胺能（DA）信号在 青春期推动奖励灵敏度提高。但是，其他机制，例如本地变化 MPFC连接性和发送给MPFC的奖励信息的变化可能正在发挥作用。在这个建议中，我们 结合化学遗传学，光遗传学，解剖学和神经钙成像，以测试如何测试 为MPFC（AIM 2）开发青春期MPFC（AIM 1）和VTA预测有助于青少年奖励 行为和影响奖励优化策略（AIM 3）。这项工作重新缩短了神经元的作用 亚型，并探测其在给定行为中的作用，是由微电路的年龄塑造的，要求 问题，细胞在青少年中是否具有与成年后相同的信息？除了值 从基础科学的角度来看，这项研究可能会产生可检验的假设来解决 为什么某些精神疾病（例如冲动控制和喂养障碍）往往会出现 青春期。钙成像，神经元活动数据分析和高级解剖技术的培训 将由导师Conor Liston博士提供，并在2光顿成像中提供其他专业知识 顾问博士。 Rajasethupathy和De Marco Garcia。沙利文博士将担任顾问 发展行为神经科学，提供有关实验设计和结果的反馈。布拉沃博士 里维拉将提供额外的行为神经科学意见，并有助于提供 向申请人提供其他职业发展培训。导师和外部咨询在一起 委员会将促进曼萨诺·尼维斯（Manzano Nieves）博士的过渡到专注于独立研究职业 揭示产后发展如何改变脑电路，以偏向行为并创造精神科 漏洞。