HIGH THROUGHPUT HOME CAGE PLATFORMS FOR INVESTIGATING NEUROPSYCHIATRIC DISORDERS IN MICE

项目摘要： 为了理解神经精神障碍，行为表型必须与改变的 大脑功能和大脑回路。然而，大多数神经精神疾病表现出一系列的 表型和高变异性使得与神经相关性的关联变得困难。 神经精神障碍如自闭症的动物模型的开发， 通过连锁分析发现基因。药物治疗也是模型 这些疾病在啮齿类动物中的表现。然而，全面的行为和生理 分析非常耗时。此外，常见的行为和生理测试是 在需要处理啮齿动物的专用设备中进行，这反过来会影响 他们的表现，并导致实验者和环境引起的变化。这就是 难以在同一动物中观察多种测量，例如行为和神经活动 并且可以捕获疾病进展的发展轨迹，和/或 治疗干预我们在这里的目标是通过开发一种新的，灵活的， 在该平台中，小鼠可以在其饲养笼环境中连续评估， 一连串的行为测试以及神经生理学测量（脑功能成像） 和光遗传学干预。 我们的系统将包括自主监测和控制大脑活动， 家庭笼子里的刺激，用于评估听觉感官处理的背景下。的 家庭笼环境与听觉学习范例的组合提供了一个单一的 培训、评估和潜在治疗操作的平台。我们的战略将 采用协作努力，建立家庭笼，最多10只小鼠/笼，可容纳 持续一年以上。在这段时间里，动物们将开始自我指导的试验， 大脑成像以及听觉处理评估。 我们的系统的一个核心特点是使用相对较小的占用空间的开源Linux- 基于计算机的工具，采用单板Raspberry Pi和Arduino计算机。这些 系统将共同努力，使灵活的家庭笼培训和评估系统。 第一个目标是完善硬件和软件，以实现跨实验室协作 然后将这些工具更广泛地传播到更广泛的神经科学社区。 我们将在特定品系的小鼠上测试家庭笼，这些小鼠先前已被证明 模拟类似自闭症的行为，并揭示行为，认知和 生理缺陷内和跨各种模型。

Project Summary: To understand neuropsychiatric disorders behavioral phenotypes have to be linked to altered brain function and brain circuits. However, most neuropsychiatric disorders show a range of phenotypes and high variability making the association with neurological correlates difficult. Development of animal models of neuropsychiatric disorders such as autism, have been facilitated by gene discovery through linkage analysis. Pharmacological treatments also model aspects of these disorders in rodents. However, comprehensive behavioral and physiological analysis is very time consuming. Moreover, common behavioral and physiological testing is performed in specialized apparatuses requiring handling of the rodents which in turn can affect their performance and lead to experimenter and environment induced variability. This it is difficult to observe multiple measures such as behavioral and neural activity in the same animal without perturbation and can capture developmental trajectories of disease progression and/or therapeutic intervention. We here aim to solve this problem by developing a new, flexible platform in which mice can be continually assessed within their home cage environments with a barrage of behavioral tests as well as neurophysiological measures (brain functional imaging) and optogenetic intervention. Our system will include autonomous monitoring and control of brain activity within these home cages in the context of stimuli used to assess auditory sensory processing. The combination of the home cage environments with auditory learning paradigms provides a single platform for both training, assessment, and potential therapeutic manipulation. Our strategy will employ a collaborative effort to build home cages for up to 10 mice/cage, which can be housed continually for up to a 1-year period. Over this time, the animals will initiate self-directed trials of brain imaging, as well as auditory processing assessments. A core feature of our system is the usage of relatively small footprint open source, Linux- based computer tools employing single board Raspberry Pi and Arduino computers. These systems will work together to enable the flexible home cage training and assessment system. The first goals are to refine the hardware and software to enable cross-laboratory collaboration and then wider dissemination of these tools to the broader neuroscience community. We will test the home cages on specific lines of mice which have previously been shown to model autistic-like behaviors and uncover co-variation of behavioral, cognitive, and physiological deficits within and across the various models.