SBIR-STTR Award

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 Statement:


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.

Project Terms:
Adult; Affect; Age; age related; Aging; American; Animals; Area; Astrocytes; base; Behavioral; Biosensor; Brain; Brain region; Cell Culture Techniques; Cells; Chemistry; Chronic; Circadian Rhythms; Computer software; Coupling; Data; design; Development; Devices; digital; Disease; effective therapy; Electrodes; Electroencephalography; Electronics; Electrophysiology (science); empowered; Epilepsy; Equipment; Etiology; Event; experience; Feedback; Fiber; Fiber Optics; Gene Mutation; Genetic; Goals; Implant; improved; Individual; innovation; insight; instrument; Knowledge; Laboratories; Lasers; Lead; Light; Longevity; Measurement; Mechanics; medical schools; Methods; middle age; Molecular; monitoring device; mouse model; multidisciplinary; Mus; Neuraxis; Neurons; Neurosciences; novel; Opsin; Optical Methods; Optics; optogenetics; Output; Phase; Physiologic Monitoring; Physiologic pulse; Physiological; Physiology; Population; Prevalence; Process; Protocols documentation; prototype; public health relevance; Rattus; Reading; Research; Research Personnel; research study; response; Rodent; Scanning; Seizures; Signal Transduction; skills; Sleep; Sleep Deprivation; Sleep Disorders; sleep epilepsy; Slow-Wave Sleep; software systems; Solutions; Source; Stereotaxic Techniques; Stimulus; System; Systems Analysis; Techniques; Technology; Time; tool; Torque; Training; Universities; Validation; Visual; Wakefulness; Wireless Technology; Work

The goal of this project is to design and commercialize tethered and wireless turn-key optogenetics and electrophysiological/neurotransmitter/behavior measurement systems for use in mice and rats. Optogenetics harnesses a combination of genetic and optical methods to directly control neuronal events in specific cells of the central nervous system. These methods are broadly applicable, but can be specifically used to provide an unprecedented understanding of cortical activity and 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 researchers 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 proposed system will be capable of delivering multiple, selectable wavelengths of light to one or more specific brain regions while simultaneously recording electrical signals, neurotransmitters and behavior 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 LED fiber probe connects via a simple electrical connection to a headstage. This removes the need for fiber optic rotary joints and enables precise control of the amount of light delivered. 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 pharmaceutical, aging and other studies.

Public Health Relevance Statement:


Public Health Relevance:
In the United States, over 1000 disorders of the brain and nervous system result in more hospitalizations than any other disease group including heart disease and cancer. Twenty-five percent of all years of life lost to disability and premature mortality are due to mental health disorders. The overall cost of serious mental illness is estimated to be $318 billion a year. The widespread use of optogenetics techniques could broadly impact the search for mitigations and cures.

NIH Spending Category:
Aging; Bioengineering; Neurosciences

Project Terms:
Aging; Animals; Area; Astrocytes; base; Behavior; behavior measurement; Behavioral; Biosensor; Brain; Brain region; burden of illness; Cannulas; Cell Culture Techniques; Cells; Chemistry; commercialization; Computer software; cost; Data; design; Development; Development Plans; Devices; digital; Disease; Electroencephalography; Electromyography; Electronics; Electrophysiology (science); Elements; Equipment; Event; experience; Feedback; Fiber; Fiber Optics; Genetic; Goals; Head; Heart Diseases; Hospitalization; improved; in vivo; Individual; Joints; Kansas; Knowledge; Laboratories; Lasers; Light; Longevity; Malignant Neoplasms; Measurement; Mechanics; Medical center; Mental disorders; Methods; multidisciplinary; Mus; Neuraxis; Neurons; Neurosciences; Neurotransmitters; New York; Operative Surgical Procedures; Opsin; Optical Methods; Optics; optogenetics; Oranges; Output; Pharmacologic Substance; Phase; Physiology; Premature Mortality; Process; product development; Progress Reports; Protocols documentation; prototype; public health relevance; Rattus; Research; Research Personnel; research study; Rodent; severe mental illness; Signal Transduction; Single Seizures; skills; software systems; Solutions; Source; Stimulus; success; System; Systems Analysis; Techniques; Time; United States; Universities; Validation; Visual; Wireless Technology; Work