权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Adolescence, motivation and the maturation of the prefrontal cortex.

青春期、动机和前额皮质的成熟。

基本信息

批准号：
10338182
负责人：
Eduardo David Leonardo
金额：
$ 51.65万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10338182
关键词：
Address Adolescence Adolescent Adult Affect Agonist Animal Model Animals Anxiety Attenuated Behavior Behavioral Brain Cells Child Childhood Costs and Benefits Data Dependence Desire for food Development Disease Fiber Future Goals Human Intervention Life Link Literature Medial Mediating Mental Depression Mental disorders Moods Motivation Mus Nature Neurons Outcome Pathway interactions Pharmaceutical Preparations Photometry Physiological Physiology Population Prefrontal Cortex Property Psychological reinforcement Rewards Schizophrenia Serotonergic System Serotonin Serotonin Receptor 5-HT1A Signal Transduction Slice Stimulus Syndrome System Taxes Testing Time Work base designer receptors exclusively activated by designer drugs dorsal raphe nucleus experimental study gain of function hedonic hippocampal pyramidal neuron in vivo loss of function mature animal motivated behavior mouse model neuroregulation postnatal development receptor receptor function response stressor willingness

项目摘要

The aim of the current proposal is to test the hypothesis that signaling through 5-HT1A receptors in the medial prefrontal cortex during adolescence is important for establishing lifelong motivation. Prior work suggests that disruption of the serotonin system during early post-natal development in animal models results in altered anxiety and mood related behaviors in the full-grown adult animal. One receptor that is particularly relevant in this regard is the 5-HT1A receptor. Recent data from our lab suggests that loss of serotonin signaling through 5-HT1A receptors in the medial prefrontal cortex during adolescence but not during adulthood, results in decreased motivation related behavioral setpoints. We hypothesize that this is true for both appetitive and avoidance motivation. The current proposal both examines mechanisms through which altered serotonin signaling through 5-HT1A receptors in adolescence leads to changes in motivation and further elucidates the specific nature of the reinforcement related behavior that is affected. In addition to a loss of function, we will use a biased 5-HT1A agonist as a gain of function approach bi-directionally modulate 5-HT1A signaling Using slice physiology, we will assess whether 5-HT1A expressing neurons alter their intrinsic properties as a result of the disrupted 5-HT1A mediated signaling, or whether there are compensatory changes in circuit properties resulting from the disruption. Using fiber photometry, we will determine how the medial prefrontal cortex engages with other circuit nodes like the dorsal raphe nucleus in tasks that tax motivational systems, with the goal of understanding the circuit basis for the disrupted behavior. Finally, we will directly assess whether the sensitivity of mPFC pyramidal neurons to inputs during adolescence is the critical factor in establishing later motivation. We will do this by manipulating mPFC principal neuron activity during the sensitive period in adolescence using DREADDS. Understanding how mPFC plasticity in adolescence can be harnessed to modulate motivation is a potentially promising strategy for addressing disorder that emerge in adolescence and often include a prominent motivational component. !

当前提案的目的是检验通过5-HT 1A的信号传导青春期内侧前额叶皮层的受体对于建立终身动力先前的研究表明，在服用维生素D的过程中，在动物模型中，出生后早期发育导致焦虑和情绪改变成年动物的相关行为。其中一种受体与在这方面是5-HT 1A受体。我们实验室的最新数据表明， 5-羟色胺信号通过5-HT 1A受体在内侧前额叶皮层青春期，而不是在成年期，导致动机相关的行为减少，设定值。我们假设，这是真实的食欲和回避的动机。目前的建议既研究了改变血清素的机制，青春期通过5-HT 1A受体的信号传导导致动机的变化，进一步阐明了强化相关行为的具体性质，影响。除了功能丧失外，我们还将使用偏向性5-HT 1A激动剂作为增益双向调节5-HT 1A信号传导使用切片生理学，我们将评估表达5-HT 1A的神经元是否会改变其内在特性， 5-HT 1A介导的信号传导被破坏的结果，或者是否存在代偿性的由中断引起的电路特性的变化。使用光纤测光，我们将决定内侧前额叶皮层如何与其他回路节点，如中缝背核的任务，税收动机系统，目标是理解中断行为的电路基础。最后，我们将直接评估青春期mPFC锥体神经元对输入的敏感性是建立日后动机的关键因素。我们将通过操纵青春期敏感期mPFC主神经元活动的研究梦想。了解青春期mPFC可塑性如何被利用，调节动机是一个潜在的有希望的解决障碍的策略，出现在青春期，往往包括一个突出的动机组成部分。 !