Poland Ryan S, Bull Cecilia, Syed Wahab A, Bowers M Scott
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine.
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine; Institute for Drug and Alcohol Studies, Departments of Psychiatry, Pharmacology, and Neuroscience, Virginia Commonwealth University School of Medicine;
J Vis Exp. 2015 Sep 16(103):53018. doi: 10.3791/53018.
Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule.
脑微量注射有助于阐明复杂行为（如动机）的分子基础。为此，啮齿动物可作为合适的模型，部分原因是人类和啮齿动物对行为相关刺激的反应以及解析刺激 - 行动结果的神经回路惊人地相似。在研究复杂行为的分子基础时，微量注射可改变、增强或沉默特定系统的试剂是一项非常有价值的技术。然而，为了便于结果的解释，微量注射部位必须精确靶向。我们提出了一种制造手术器械和微量注射针的方法，该方法能够以最小的成本实现精确的微量注射和无限的定制性。重要的是，如果与其他涵盖必要手术程序的《可视实验教程》文章一起进行，这项技术可以在清醒的啮齿动物身上成功完成。此外，有许多行为范式非常适合测量动机。渐进比率是一种常用的方法，它量化了强化物在工作要求（通常呈指数级）不断增加的情况下维持反应的效力。该实验对强化物强度和药理学操作敏感，这使得可以确定强化效力和/或动机。我们还提出了一种直接的方法来编写操作软件程序，以适应渐进比率强化程序。
