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. !

当前建议的目的是测试通过5-HT1A发出信号的假设青春期内侧前额叶皮层中的受体对于建立很重要终身动机。先前的工作表明，在动物模型的产后早期发育会导致焦虑和情绪改变成年动物的相关行为。一个特别相关的受体在这方面是5-HT1A受体。我们实验室的最新数据表明丢失通过5-HT1A受体在内侧前额叶皮层中的5-羟色胺信号传导。青春设定点。我们假设对欲望和回避动机都是如此。当前的提案两者都检查了改变5-羟色胺的机制青春期通过5-HT1A受体通过5-HT1A受体传导会导致动机和进一步阐明了相关行为的特定性质做作的。除功能丧失外，我们还将使用偏见的5-HT1A激动剂作为增益功能方法双向调节5-HT1A信号传导，使用切片生理学，我们将评估5-HT1A表达神经元是否会改变其内在特性 5-HT1A介导的信号传导中断的结果，或者是否有补偿性中断导致电路属性的变化。使用纤维光度法，我们将确定内侧前额叶皮层如何与其他电路节点互动在征收动机系统的任务中的背raphe核，目的是了解破坏行为的电路基础。最后，我们将直接评估MPFC锥体神经元对青春期输入的敏感性是否是建立以后动机的关键因素。我们将通过操纵 MPFC主神经元在青春期敏感时期使用恐怖。了解如何利用MPFC的可塑性调节动机是解决障碍的潜在有前途的策略在青春期出现，通常包括一个突出的动机组成部分。呢