Age-related sleep problems such as advanced sleep phase disorder (ASPD) are estimated to affect at least 1% of middle-aged adults and increase in prevalence with age. While the detrimental effects of sleep disruption with aging are well characterized, detailed insights into the molecular and physiological mechanisms underlying these sleep changes are greatly lacking. Optogenetics harnesses a combination of genetic and optical methods to directly control neuronal events in specific cells of the central nervous system. Recent studies have confirmed that control of both wakefulness and slow-wave-sleep are possible using optogenetic methods. These methods can be used to provide an unprecedented understanding of cortical activity in aging. The optogenetics field is maturing and there are numerous commercial sources for optogenetic components;however, the technique requires a multidisciplinary skill set including chemistry, optics, physiology, electronics, mechanics, software, and systems analysis. To date, any single experiment requires a system designed from individual, component parts. Many labs also have existing equipment that they desire to incorporate into a full optogenetics system. This may include lasers, cameras and potentially behavioral hardware and software platforms. In these situations a digital timing protocol (TTL) is often used to maintain synchronization, but there are subtleties (device latency, etc.) to this approach that are often overlooked. The goal of this project is to combine optogenetics and electrophysiological recording into a single turn-key, modular system for mice. The system will be capable of delivering multiple, selectable wavelengths of light to one or more specific brain regions while simultaneously recording electrical signals in rodents throughout the lifespan of the animal. All synchronization between the electrophysiological, mechanical and visual inputs, and optical and stimulus outputs will be precisely controlled via a master timing, digital input/output platform as well as sophisticated software timing techniques. The optogenetics light source and coupling fiber will be implemented on a standardized probe platform that can be easily, and accurately, implanted using stereotaxic techniques. When completed, this system will significantly improve scientific knowledge by providing a turn-key solution for researchers from multiple fields to seamlessly integrate optogenetic control alongside traditional aging and EEG-based studies.

Public Health Relevance

Disrupted sleep and epilepsy are both disorders evaluated using electroencephalography. It is estimated that at least 50 to 70 million Americans suffer each year from chronic sleep and circadian disorders while epilepsy is estimated to affect as much as 1% of the population. The development of a turn-key solution for optogenetic manipulation of cortical activity will empower researchers to better understand sleep and seizure etiology and lead to more effective treatments.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-ETTN-A (10))
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Wise, Bradley C
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Pinnacle Technology, Inc
United States
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