A wirelessly powered and controlled device for optical neural control of freely-behaving animals

Optogenetics, the ability to use light to activate and silence specific neuron types within neural networks in vivo and in vitro, is revolutionizing neuroscientists' capacity to understand how defined neural circuit elements contribute to normal and pathological brain functions. Typically, awake behaving experiments are conducted by inserting an optical fiber into the brain, tethered to a remote laser, or by utilizing an implanted light-emitting diode (LED), tethered to a remote power source. A fully wireless system would enable chronic or longitudinal experiments where long duration tethering is impractical, and would also support high-throughput experimentation. However, the high power requirements of light sources (LEDs, lasers), especially in the context of the extended illumination periods often desired in experiments, precludes battery-powered approaches from being widely applicable. We have developed a headborne device weighing 2 g capable of wirelessly receiving power using a resonant RF power link and storing the energy in an adaptive supercapacitor circuit, which can algorithmically control one or more headborne LEDs via a microcontroller. The device can deliver approximately 2 W of power to the LEDs in steady state, and 4.3 W in bursts. We also present an optional radio transceiver module (1 g) which, when added to the base headborne device, enables real-time updating of light delivery protocols; dozens of devices can be controlled simultaneously from one computer. We demonstrate use of the technology to wirelessly drive cortical control of movement in mice. These devices may serve as prototypes for clinical ultra-precise neural prosthetics that use light as the modality of biological control.National Institutes of Health (U.S.) (NIH Director’s New Innovator Award (DP2OD002002))National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1RC2DE020919)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 1R43NS070453)National Science Foundation (U.S.) (CAREER award)National Science Foundation (U.S.) (NSF Grant DMS 1042134)National Science Foundation (U.S.) (NSF Grant DMS 0848804)National Science Foundation (U.S.) (NSF Grant EFRI 0835878)Benesse FoundationGoogle (Firm)Dr. Gerald Burnett and Marjorie BurnettUnited States. Dept. of Defense (CDMRP PTSD Program)Massachusetts Institute of TechnologyBrain & Behavior Research FoundationAlfred P. Sloan FoundationSociety for NeuroscienceMassachusetts Institute of Technology. Media LaboratoryMcGovern Institute for Brain Research at MITWallace H. Coulter Foundatio

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men. Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period. Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men. In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress. © 2014 Informa UK, Ltd

Area selection for diamonds using magnetotellurics : examples from southern Africa

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Lithos 112 (2009): 83-92, doi:10.1016/j.lithos.2009.06.011.Southern Africa, particularly the Kaapvaal Craton, is one of the world’s best natural laboratories for studying the lithospheric mantle given the wealth of xenolith and seismic data that exist for it. The Southern African Magnetotelluric Experiment (SAMTEX) was launched to complement these databases and provide further constraints on physical parameters and conditions by obtaining information about electrical conductivity variations laterally and with depth. Initially it was planned to acquire magnetotelluric data on profiles spatially coincident with the Kaapvaal Seismic Experiment, however with the addition of seven more partners to the original four through the course of the experiment, SAMTEX was enlarged from two to four phases of acquisition, and extended to cover much of Botswana and Namibia. The complete SAMTEX dataset now comprises MT data from over 675 distinct locations in an area of over one million square kilometres, making SAMTEX the largest regional-scale MT experiment conducted to date. Preliminary images of electrical resistivity and electrical resistivity anisotropy at 100 km and 200 km, constructed through approximate one-dimensional methods, map resistive regions spatially correlated with the Kaapvaal, Zimbabwe and Angola Cratons, and more conductive regions spatially associated with the neighbouring mobile belts and the Rehoboth Terrain. Known diamondiferous kimberlites occur primarily on the boundaries between the resistive or isotropic regions and conductive or anisotropic regions. Comparisons between the resistivity image maps and seismic velocities from models constructed through surface wave and body wave tomography show spatial correlations between high velocity regions that are resistive, and low velocity regions that are conductive. In particular, the electrical resistivity of the sub-continental lithospheric mantle of the Kaapvaal Craton is determined by its bulk parameters, so is controlled by a bulk matrix property, namely temperature, and to a lesser degree by iron content and composition, and is not controlled by contributions from interconnected conducting minor phases, such as graphite, sulphides, iron oxides, hydrous minerals, etc. This makes quantitative correlations between velocity and resistivity valid, and a robust regression between the two gives an approximate relationship of Vs [m/s] = 0.045*log(resistivity [ohm.m]).We especially thank our academic funding sponsors; the Continental Dynamics programme of the U.S. National Science Foundation, the South African Department of Science and Technology, and Science Foundation Ireland

Risk factors for ischaemic heart disease in a Cretan rural population: a twelve year follow-up study

<p>Abstract</p> <p>Background</p> <p>Crete has been of great epidemiological interest ever since the publication of the Seven Countries Study. In 1988 a well-defined area of rural Crete was studied, with only scarce signs of coronary heart disease (CHD) despite the unfavorable risk profile. The same population was re-examined twelve years later aiming to describe the trends of CHD risk factors over time and discuss some key points on the natural course of coronary heart disease in a rural population of Crete.</p> <p>Methods and Results</p> <p>We re-examined 200 subjects (80.7% of those still living in the area, 62.4 ± 17.0 years old). The prevalence of risk factors for CHD was high with 65.9% of men and 65.1% of women being hypertensive, 14.3% of men and 16.5% of women being diabetic, 44% of men being active smokers and more than 40% of both sexes having hyperlipidaemia. Accordingly, 77.5% of the population had a calculated Framingham Risk Score (FRS) ≥ 15%, significantly higher compared to baseline (p < 0.001). The overall occurrence rate for CHD events was calculated at 7.1 per 1000 person-years (95% confidence interval: 6.8–7.3).</p> <p>Conclusion</p> <p>The study confirms the unfavorable risk factor profile of a well defined rural population in Crete. Its actual effect on the observed incidence of coronary events in Cretans remains yet to be defined.</p

Photolysis of a caged peptide reveals rapid action of NSF prior to neurotransmitter release

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 105 (2008): 347-352, doi:10.1073/pnas.0707197105.The time at which the N-ethylmaleimide-sensitive factor (NSF) acts during synaptic vesicle trafficking was identified by time-controlled perturbation of NSF function with a photo-activatable inhibitory peptide. Photolysis of this caged peptide in the squid giant presynaptic terminal caused an abrupt (0.2 s) slowing of the kinetics of the postsynaptic current (PSC) and a more gradual (2-3 s) reduction in PSC amplitude. Based on the rapid rate of these inhibitory effects relative to the speed of synaptic vesicle recycling, we conclude that NSF functions in reactions that immediately precede neurotransmitter release. Our results indicate the locus of SNARE protein recycling in presynaptic terminals and reveal a new target for rapid regulation of transmitter release.T.K. was supported by a Grass Fellowship in Neuroscience, an HFSP long-term fellowship and the Feodor-Lynen Program of the Alexander von Humboldt Foundation. Y.L. received a American Heart Association predoctoral fellowship. The research also was supported by NIH NS-21624

Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

Synapse Clusters Are Preferentially Formed by Synapses with Large Recycling Pool Sizes

Synapses are distributed heterogeneously in neural networks. The relationship between the spatial arrangement of synapses and an individual synapse's structural and functional features remains to be elucidated. Here, we examined the influence of the number of adjacent synapses on individual synaptic recycling pool sizes. When measuring the discharge of the styryl dye FM1–43 from electrically stimulated synapses in rat hippocampal tissue cultures, a strong positive correlation between the number of neighbouring synapses and recycling vesicle pool sizes was observed. Accordingly, vesicle-rich synapses were found to preferentially reside next to neighbours with large recycling pool sizes. Although these synapses with large recycling pool sizes were rare, they were densely arranged and thus exhibited a high amount of release per volume. To consolidate these findings, functional terminals were marked by live-cell antibody staining with anti-synaptotagmin-1-cypHer or overexpression of synaptopHluorin. Analysis of synapse distributions in these systems confirmed the results obtained with FM 1–43. Our findings support the idea that clustering of synapses with large recycling pool sizes is a distinct developmental feature of newly formed neural networks and may contribute to functional plasticity

A historical perspective on the discovery of statins

Cholesterol is essential for the functioning of all human organs, but it is nevertheless the cause of coronary heart disease. Over the course of nearly a century of investigation, scientists have developed several lines of evidence that establish the causal connection between blood cholesterol, atherosclerosis, and coronary heart disease. Building on that knowledge, scientists and the pharmaceutical industry have successfully developed a remarkably effective class of drugs—the statins—that lower cholesterol levels in blood and reduce the frequency of heart attacks