Implications of Prefrontal Cortex Development for Adolescent Reward Seeking Behavior

项目总结 随着年龄的增长，我们学会了调整自己的行为，以优化奖励结果。这些适应性选择包括 由当前的感觉条件、内部认知状态和未来预期来协调。在青春期， 奖励将感觉刺激的外围检测与参与决策的中央电路联系起来的电路 激励状态继续增长，重塑了内侧前额叶内的微回路连接 皮质(MPFC)。这种发展可以解释为什么青少年表现出更强的冲动和 降低了行为灵活性，未能优化奖励结果。然而，发展变化 在奖赏环路中，人们对青春期奖赏学习的差异知之甚少。 MPFC是情绪调节、决策和寻求奖励的关键区域。奖赏是- MPFC的调制特性来源于腹侧被盖区(VTA)的输入。在.期间 青春期，VTA对mPFC的输入仍在发育中，而这些发育对功能的影响 变化是未知的。一种有影响力的理论认为，脑内多巴胺能(DA)信号的增加 青春期会提高对奖励的敏感度。然而，其他机制，如在当地的变化 MPFC连接和发送到mPFC的奖励信息的变化可能起作用。在这项提案中，我们 使用化学遗传学、光遗传学、解剖学和神经钙素成像的组合来测试 发展青少年mPFC(目标1)和VTA投射到mPFC(目标2)有助于青少年奖励 行为和影响奖励优化策略(目标3)。这项工作重新构建了神经元的角色。 子类型，并探测它们在给定行为中的作用是否由微电路的年龄决定，询问 问题是，青少年时期的细胞携带的信息与成年时相同吗？除了价值之外 从基础科学的角度来看，这项研究可能会产生可检验的假说，以解决 为什么某些精神障碍，如冲动控制和进食障碍，往往会在 青春期。钙成像、神经元活动数据分析和高级解剖技术方面的培训 将由导师Conor Liston博士提供，并由 顾问拉贾塞图帕西和德马尔科·加西亚。沙利文博士将担任 发展行为神经科学，提供对实验设计和结果的反馈。布拉沃博士 Rivera将提供一个额外的行为神经科学观点，并将在提供 为申请者提供额外的职业发展培训。共同指导和外部咨询 委员会将推动曼扎诺·尼维斯博士过渡到专注于 揭示出生后发育如何改变大脑回路以偏向行为并创造精神障碍 漏洞。

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.