Neural Processing in Behaving Adolescent Rats

描述(由申请人提供)：本申请概述了一项培训计划和实验程序，以确保申请人将接受技术和智力的发展，走向独立。该应用侧重于青少年动机行为的神经元基础，这是一个对基础科学和公共卫生具有重要影响的主题。青少年特别容易患上毒瘾和其他精神病态疾病。这种脆弱性可能是青春期前额叶皮质(PFC)和纹状体发育的结果。然而，关于动机行为表达过程中这些脑区的神经元活动如何随着年龄的变化而不同，我们知之甚少。申请人已经开发了线索反应抑制任务，或CRIT，以测量在抑制线索期间抑制反应，然后在线索终止后迅速反应的能力。初步数据显示，在线索终止后，青春期大鼠不能像成年大鼠那样快速反应，这种行为差异似乎与无法充分维持对线索的注意力有关。据推测，与成年大鼠相比，这种行为特征与青春期大鼠PFC和纹状体亚区任务事件的神经元编码异常有关。为了验证这一假设，本文提出了两个目标，这两个目标都涉及到对申请者来说是新颖的方法和数据分析的应用。第一个目标是 选择这两个区域是因为先前的啮齿动物记录研究表明，扣带回的相反应与持续的注意有关，而且青少年和成年人在动机行为中，扣带回的神经元编码不同。神经活动将在线索呈现、工具性反应和结果预期/交付过程中进行分析，然后在成人和青少年之间进行比较。在第二个目标中，将量化ACC和DS内的神经元相互作用，以及在CRIT期间ACC和DS之间的通信。这将涉及单元对之间的噪声相关性、局部场势(LFP)频谱功率的区域内和区域之间的分析，以及单个单元活动和LFP之间的锁相。这将提供有关ACC和DS之间的通信和信息流方向的信息，以及这如何与青少年和成年大鼠的行为有关。总而言之，这些实验将提供关于成年和青少年大鼠之间神经处理的不同，以及这些差异如何与年龄相关的行为差异相关的新信息。

DESCRIPTION (provided by applicant): This application outlines a training plan and experimental procedures to ensure that the applicant will receive technical and intellectual development toward independence. The application focuses on neuronal bases of motivated behavior in adolescents, a topic with important implications for basic science and public health. Adolescents are particularly vulnerable to drug addiction and other psychopathological illnesses. This vulnerability may be a result of ongoing prefrontal cortex (PFC) and striatal development during adolescence. However, little is known about how neuronal activity within these brain regions during the expression of motivated behavior differs as a function of age. The applicant has developed the Cued Response Inhibition Task, or CRIT, to measure the ability to withhold a response during an inhibitory cue, then respond promptly following cue termination. Preliminary data demonstrate that adolescent rats are unable to respond as quickly as adults following cue termination, a behavioral difference that appears to be related to inability to adequately sustain attention to the cue. It is hypothesized that this behavioral profile will be associated with aberrant neuronal encoding of task events in PFC and striatal subregions in adolescent compared to adult rats. To test this hypothesis, two aims are proposed, both of which involve application of methodologies and data analysis that are novel for the applicant. The first aim will involve recording single unit activity simultaneously from two brain regions during CRIT performance: anterior cingulate cortex (ACC) and dorsal striatum (DS), These regions were chosen because previous rodent recording studies demonstrate that ACC phasic responses correlate with sustained attention, and that neuronal encoding in the DS differs in adolescents from adults during motivated behavior. Neural activity will be analyzed during cue presentation, instrumental response, and outcome expectation/delivery, then compared between adults and adolescents. In the second aim, neuronal interactions within ACC and DS, as well as communication between ACC and DS during CRIT will be quantified. This will involve within, and between region analysis of noise correlations between unit pairs, local field potential (LFP) spectral power, and phase-locking between single unit activity and LFP. This will provide information about communication and direction of information flow between ACC and DS, and how this relates to behavior in adolescent and adult rats. Collectively, these experiments will provide novel information on how neural processing differs between adult and adolescent rats, and how these differences correlate with age related behavioral differences.