HIGH THROUGHPUT HOME CAGE PLATFORMS FOR INVESTIGATING NEUROPSYCHIATRIC DISORDERS IN MICE

项目总结： 要了解神经精神障碍，行为表型必须与改变有关 大脑功能和大脑回路。然而，大多数神经精神障碍表现为一系列 表型和高度的变异性使得与神经学相关性的联系变得困难。 自闭症等神经精神障碍动物模型的发展 通过连锁分析发现基因。药物治疗也是一种模式 啮齿类动物的这些紊乱的各个方面。然而，综合行为和生理 分析是非常耗时的。此外，常见的行为和生理测试是 在需要处理啮齿动物的专门设备中进行，这反过来可能会影响 它们的性能和导致实验者和环境引起的变异性。就是这个了 很难观察到同一动物的行为和神经活动等多项指标 不受干扰，可以捕捉疾病进展和/或发展轨迹 治疗性干预。我们的目标是通过开发一种新的、灵活的 一个平台，可以在老鼠的家庭笼子环境中通过 接二连三的行为测试和神经生理测量(脑功能成像) 以及光遗传干预。 我们的系统将包括对大脑活动的自主监测和控制 家庭笼子中的刺激被用来评估听觉感觉加工。这个 家庭笼子环境与听觉学习范例的结合提供了单一的 培训、评估和潜在治疗操作的平台。我们的战略将 利用协作努力建造最多10只老鼠/笼的家庭笼子，这些笼子可以容纳 持续最长1年的时间。在这段时间里，这些动物将启动自我指导的试验 大脑成像，以及听觉处理评估。 我们系统的一个核心特征是使用了相对较小的开源Linux- 基于使用单板Raspberry Pi和Arduino计算机的计算机工具。这些 各系统将协同工作，以实现灵活的家笼培训和评估系统。 第一个目标是改进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给更广泛的神经科学界。 我们将在之前展示的特定品系的小鼠身上测试家庭笼子 模拟孤独症样行为并揭示行为、认知和行为的协变 各种模型内部和各模型之间的生理缺陷。

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.