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

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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.