OptoPAD, a closed-loop optogenetics system to study the circuit basis of feeding behaviors.
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ABSTRACT:
SUBMITTER: Moreira JM
PROVIDER: S-EPMC6589098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice.
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Project description:Overdoses from non-medical use of opioids can lead to hypoxemic/hypercarbic respiratory failure, cardiac arrest, and death when left untreated. Opioid toxicity is readily reversed with naloxone, a competitive antagonist that can restore respiration. However, there remains a critical need for technologies to administer naloxone in the event of unwitnessed overdose events. We report a closed-loop wearable injector system that measures respiration and apneic motion associated with an opioid overdose event using a pair of on-body accelerometers, and administers naloxone subcutaneously upon detection of an apnea. Our proof-of-concept system has been evaluated in two environments: (i) an approved supervised injection facility (SIF) where people self-inject opioids under medical supervision and (ii) a hospital environment where we simulate opioid-induced apneas in healthy participants. In the SIF (n = 25), our system identified breathing rate and post-injection respiratory depression accurately when compared to a respiratory belt. In the hospital, our algorithm identified simulated apneic events and successfully injected participants with 1.2 mg of naloxone. Naloxone delivery was verified by intravenous blood draw post-injection for all participants. A closed-loop naloxone injector system has the potential to complement existing evidence-based harm reduction strategies and, in the absence of bystanders, help make opioid toxicity events functionally witnessed and in turn more likely to be successfully resuscitated.
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Project description:Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production1-5. While many neural circuits underlying feeding and parenting behaviors are well characterized6-9, it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARCAgRP neurons directly inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that governs both parenting and satiety. Selective activation of this ARCAgRP to MPOABRS3 circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.
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Project description:Feeding is an essential part of animal life that is greatly impacted by the sense of taste. Although the characterization of taste-detection at the periphery has been extensive, higher order taste and feeding circuits are still being elucidated. Here, we use an automated closed-loop optogenetic activation screen to detect novel taste and feeding neurons in Drosophila melanogaster. Out of 122 Janelia FlyLight Project GAL4 lines preselected based on expression pattern, we identify six lines that acutely promote feeding and 35 lines that inhibit it. As proof of principle, we follow up on R70C07-GAL4, which labels neurons that strongly inhibit feeding. Using split-GAL4 lines to isolate subsets of the R70C07-GAL4 population, we find both appetitive and aversive neurons. Furthermore, we show that R70C07-GAL4 labels putative second-order taste interneurons that contact both sweet and bitter sensory neurons. These results serve as a resource for further functional dissection of fly feeding circuits.
| S-EPMC8104954 | biostudies-literature
Project description:Objective.Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus.Approach.Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers.Results.The CLARA system tracks unconstrained skilled reach behavior in 3D at 150 Hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with short latency. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that learning selectively improves reach failures but does not alter the kinematics of successful reaches. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) improves skilled reach performance and increases reach trajectory consistency in healthy animals.Significance.The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our investigating the role of closed-loop VNS stimulation on motor performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.
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Project description:Background Drug closed-loop management reflects the level of hospital management and pharmacist service. It is a challenge for hospital pharmacists to realize the whole-process closed-loop management of drugs in hospital pharmacies. Therefore, this study aimed to evaluate the operational effect of using mobile technology to build a closed-loop drug management system. Methods Using mobile technology, replacing the traditional paper dispensing model and constructing a multinode information collection system according to the Healthcare Information and Management Systems Society Standard, we reformed the hospital information system and inpatient pharmacy workflow and then evaluated the new approach using statistical methods. Results After the transformation, the entire process of drug data can be traced. Closed-loop management, as well as real-time data verification and control, thereby improves the work efficiency and reduces the drug dispensing time. By reducing the work error rate, the number of dispensing errors decreased from 5 to 1 case/month. The comprehensive dispensing process can achieve the whole workflow of paperless operation and reduce the use of paper A4 by 180,000 pieces per year. Conclusions Mobile technology can improve the service level of pharmacies, enhance the level of drug management and hospital quality management, ensure the safety of medication for inpatients, and significantly reduce the amount of paper used. Supplementary Information The online version contains supplementary material available at 10.1186/s12911-022-02067-2.
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Project description:The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.
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Project description:Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-? onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders.
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Project description:BackgroundThis feasibility study investigated the insulin-delivery characteristics of the Hypoglycemia-Hyperglycemia Minimizer (HHM) System-an automated insulin delivery device-in participants with type 1 diabetes.MethodsThirteen adults with type 1 diabetes were enrolled in this nonrandomized, uncontrolled, clinical-research-center-based feasibility study. The HHM System comprised a continuous subcutaneous insulin infusion pump, a continuous glucose monitor (CGM), and a model predictive control algorithm with a safety module, run on a laptop platform. Closed-loop control lasted approximately 20 hours, including an overnight period and two meals.ResultsWhen attempting to minimize glucose excursions outside of a prespecified target zone, the predictive HHM System decreased insulin infusion rates below the participants' preset basal rates in advance of below-zone excursions (CGM < 90 mg/dl), and delivered 80.4% less insulin than basal during those excursions. Similarly, the HHM System increased infusion rates above basal during above-zone excursions (CGM > 140 mg/dl), delivering 39.9% more insulin than basal during those excursions. Based on YSI, participants spent a mean ± standard deviation (SD) of 0.2 ± 0.5% of the closed-loop control time at glucose levels < 70 mg/dl, including 0.3 ± 0.9% for the overnight period. The mean ± SD glucose based on YSI for all participants was 164.5 ± 23.5 mg/dl. There were nine instances of algorithm-recommended supplemental carbohydrate administrations, and there was no severe hypoglycemia or diabetic ketoacidosis.ConclusionsResults of this study indicate that the current HHM System is a feasible foundation for development of a closed-loop insulin delivery device.
| S-EPMC4454115 | biostudies-literature