NCS-FO: Integrative Approaches to Study the Role of Early Life Sleep Disruption in Brain Development and Autistic Behaviors

早期生活睡眠中断（ELSD）已被证明会影响动物复杂社会行为的发展，损害草原田鼠之间的社会联系，其方式让人想起人类的自闭症。为了了解大脑发育的潜在变化，迫切需要开发创新的工具，在两个或更多动物之间复杂的社会互动中实时测量神经递质水平。在这个项目中，研究小组将设计、实施和测试新型集成生物传感器微探针，该探针将在复杂的社会互动中实时记录两种关键的脑神经递质（l -谷氨酸，一种兴奋性神经递质，伽马氨基丁酸，一种抑制性神经递质）。生物传感器系统将无线化，还将与脑电图（EEG）相结合，作为脑电活动的测量方法。这个高度合作的项目通过开发一种急需的方法来实时测量大脑中的兴奋：抑制（E:I）平衡，从而推进了神经工程，这将为健康和自闭症个体的大脑控制社会互动的基本问题提供信息。本研究的具体任务如下：任务1)开发和测试有线，基于酶的柔性集成双传感器探针，以评估草原田鼠的l-谷氨酸和GABA水平，以检查在复杂的社会互动中大脑中的E:I平衡。开发并测试一个集成了l-谷氨酸和GABA柔性双传感器探头的无线系统，以研究复杂社会互动中大脑E:I平衡的变化。开发和测试与EEG集成的无线双传感器探头，作为研究ELSD对EEG伽马振荡的影响的一种方式，作为复杂社会互动中E:I平衡的功能读数。在这个项目中开发的微探针和系统可以推广到其他使用啮齿动物或更大动物模型的神经系统疾病研究中。这一结果将有助于揭示神经发育障碍中神经过程是如何出错的，并使下一代神经假体、治疗方法和脑机接口成为可能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Early life sleep disruption (ELSD) has been shown to affect the development of complex social behaviors in animals, impairing social bonding between prairie voles in a manner reminiscent of autism in humans. In order to understand the underlying changes in brain development, there is a dire need to develop innovative tools that can measure neurotransmitter levels in real-time during complex social interactions among two or more animals. In this project, the research team will design, implement and test novel integrated biosensor microprobes that will simultaneously record two key brain neurotransmitters (L-glutamate, an excitatory neurotransmitter, and Gamma Aminobutyric Acid [GABA], an inhibitory neurotransmitter) in real time during complex social interactions using this vole model of autism. The biosensor system will be made wireless and will also be combined with electroencephalography (EEG), as a measure of brain electrical activity. This highly collaborative project advances neuroengineering by developing a much-needed method to measure Excitation:Inhibition (E:I) balance in the brain in real-time, which will inform fundamental questions about the brain control of social interactions in healthy and autistic individuals.The specific tasks of this study are as follows: Task 1) Develop and test wired, enzyme-based flexible integrated dual-sensor probes to assess L-glutamate and GABA levels in prairie voles in order to examine E:I balance in the brain during complex social interactions. Task 2) Develop and test a wireless system with an integrated L-glutamate and GABA flexible dual-sensor probe to study changes in the E:I balance the brain during complex social interactions. Task 3) Develop and test a wireless dual sensor probe integrated with EEG as a way to investigate effects of ELSD on EEG gamma oscillations as a functional readout of E:I balance during complex social interactions. The microprobes and systems developed in this project can be generalized to other studies of neurological disorders using rodents or larger animal models. The outcomes would help reveal how neural processes may go awry in neurodevelopmental disorders, as well as enable the next generation of neural prostheses, therapeutics and brain machine interfaces.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.