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
基本信息
- 批准号:10739548
- 负责人:
- 金额:$ 11.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdolescenceAdolescentAdolescent BehaviorAdolescent DevelopmentAdultAdvisory CommitteesAgeAnatomyAnimal ModelAnimalsAreaAtlasesBasic ScienceBehaviorBehavioralBiological MarkersBrainCalciumCellsCodeCognitiveCommunitiesCuesDataData AnalysesDecision MakingDetectionDevelopmentDiscriminationDiseaseEquilibriumExhibitsExperimental DesignsFailureFeedbackFiberFutureGeneticGlutamatesImageImpulsivityInfluentialsLearningLifeLinkLongitudinal StudiesMedialMental disordersMentorsMotivationMusNeuronsNeurosciencesOutcomePeripheralPhasePhotometryPlayPrefrontal CortexPropertyRegulationResearchRewardsRoleSensoryShapesSignal TransductionSucroseTask PerformancesTechniquesTestingTrainingVentral Tegmental AreaWorkage relatedanatomical tracingbehavior changecareercareer developmentcell cortexdesignearly adolescenceemotion regulationexpectationfeedingflexibilityhuman modelinsightneuralneuronal circuitryoptogeneticspostnatal developmentresponsesensory stimulustheoriestooltransmission processtwo-photon
项目摘要
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,我们学会调整我们的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所协调。在青春期,
将感觉刺激的外围检测与参与决策的中央回路联系起来的奖励回路
动机状态持续增长,重塑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性,
行为灵活性减弱,并且未能优化奖励结果。然而,发展变化
在奖励回路中,青少年时期奖励学习的差异还知之甚少。
mPFC是情绪调节、决策和寻求奖励的关键区域。奖励-
mPFC的调制特性源自来自腹侧被盖区(VTA)的输入。期间
在青少年时期,VTA对mPFC的输入仍在发展中,这些发育的功能影响
变化未知。一个有影响力的理论表明,增加多巴胺(DA)信号,
青春期促使奖励敏感度提高。然而,其他机制,如当地的变化,
mPFC连接和发送到mPFC的奖励信息的变化可能起作用。在本提案中,我们
使用化学遗传学,光遗传学,解剖学和神经钙成像的组合,以测试
发展青少年mPFC(目标1)和VTA对mPFC(目标2)的预测有助于青少年的奖励
行为和影响奖励优化策略(目标3)。这项工作重新定义了神经元的作用
子类型,并探测它们在给定行为中的作用是否受微电路年龄的影响,
问题是,青少年的细胞携带的信息和成年人的一样吗?除了该值
从基础科学的角度来看,这项研究可能会产生可验证的假设,
为什么某些精神疾病,如冲动控制和进食障碍,往往出现在
青春期钙成像、神经元活动数据分析和高级解剖技术培训
将由导师Conor Liston博士提供,并由
拉贾斯坦邦医生和德马尔科·加西亚医生。沙利文博士将担任顾问,
发展行为神经科学,提供实验设计和结果的反馈。布拉沃医生
里维拉将提供一个额外的行为神经科学的角度,并将有助于提供
为申请人提供额外的职业发展培训。导师和外部顾问一起
委员会将促进曼萨诺尼维斯博士过渡到一个独立的研究生涯,重点是
揭示了出生后的发育如何改变大脑回路,从而使行为产生偏见,
漏洞
项目成果
期刊论文数量(0)
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Gabriela Manzano Nieves其他文献
Gabriela Manzano Nieves的其他文献
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{{ truncateString('Gabriela Manzano Nieves', 18)}}的其他基金
Effects of early life stress on functional development of prefrontal-amygdala connectivity
早期生活压力对前额叶-杏仁核连接功能发育的影响
- 批准号:
10064881 - 财政年份:2020
- 资助金额:
$ 11.25万 - 项目类别:
Effects of early life stress on functional development of prefrontal-amygdala connectivity
早期生活压力对前额叶-杏仁核连接功能发育的影响
- 批准号:
10550187 - 财政年份:2020
- 资助金额:
$ 11.25万 - 项目类别:
Effects of early life stress on functional development of prefrontal-amygdala connectivity
早期生活压力对前额叶-杏仁核连接功能发育的影响
- 批准号:
10328237 - 财政年份:2020
- 资助金额:
$ 11.25万 - 项目类别:
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