Neural Processing in Behaving Adolescent Rats

描述（由申请人提供）：本申请概述了培训计划和实验程序，以确保申请人将获得独立的技术和智力发展。该应用程序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意义的主题。青少年特别容易染上毒瘾和其他精神疾病。这种脆弱性可能是青春期前额叶皮层（PFC）和纹状体发育的结果。然而，很少有人知道这些大脑区域内的神经元活动在表达动机行为时如何随着年龄的变化而变化。申请人开发了线索反应抑制任务（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。初步数据表明，青少年大鼠无法迅速响应成年人以下的线索终止，行为的差异，似乎与无法充分维持注意力的线索。据推测，这种行为的配置文件将与异常的神经元编码的任务事件在青少年的PFC和纹状体亚区相比，成年大鼠。为了验证这一假设，提出了两个目标，这两个目标都涉及到申请人新颖的方法和数据分析的应用。第一个目标将 涉及在CRIT表现期间同时记录来自两个脑区域的单个单元活动：前扣带皮层（ACC）和背侧纹状体（DS）。选择这些区域是因为先前的啮齿动物记录研究表明ACC阶段性反应与持续注意力相关，并且DS中的神经元编码在动机行为期间在青少年与成人中不同。神经活动将在提示呈现，工具反应和结果预期/交付期间进行分析，然后在成人和青少年之间进行比较。在第二个目标中，ACC和DS内的神经元相互作用，以及在CRIT期间ACC和DS之间的通信将被量化。这将涉及区域内和区域之间对单元对之间的噪声相关性、局部场电位（LFP）谱功率以及单个单元活动和LFP之间的锁相进行分析。这将提供有关ACC和DS之间信息流的沟通和方向的信息，以及这与青少年和成年大鼠行为的关系。总的来说，这些实验将提供关于成年大鼠和青少年大鼠之间神经处理差异的新信息，以及这些差异如何与年龄相关的行为差异相关。

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.