1,721,007 research outputs found
A history of optogenetics: the development of tools for controlling brain circuits with light
No full textUnderstanding how different kinds of neuron in the brain work together to implement sensations, feelings, thoughts, and movements, and how deficits in specific kinds of neuron result in brain diseases, has long been a priority in basic and clinical neuroscience. “Optogenetic” tools are genetically encoded molecules that, when targeted to specific neurons in the brain, enable their activity to be driven or silenced by light. These molecules are microbial opsins, seven-transmembrane proteins adapted from organisms found throughout the world, which react to light by transporting ions across the lipid membranes of cells in which they are genetically expressed. These tools are enabling the causal assessment of the roles that different sets of neurons play within neural circuits, and are accordingly being used to reveal how different sets of neurons contribute to the emergent computational and behavioral functions of the brain. These tools are also being explored as components of prototype neural control prosthetics capable of correcting neural circuit computations that have gone awry in brain disorders. This review gives an account of the birth of optogenetics and discusses the technology and its applications.National Institutes of Health (U.S.) (New Innovator Award (DP2OD002002))National Science Foundation (U.S.) (EFRI 0835878)National Science Foundation (U.S.) (DMS 0848804)National Science Foundation (U.S.) (DMS 1042134)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)United States. Dept. of Defense (CDMRP PTSD Program
Principles of designing interpretable optogenetic behavior experiments
No full textOver the last decade, there has been much excitement about the use of optogenetic tools to test whether specific cells, regions, and projection pathways are necessary or sufficient for initiating, sustaining, or altering behavior. However, the use of such tools can result in side effects that can complicate experimental design or interpretation. The presence of optogenetic proteins in cells, the effects of heat and light, and the activity of specific ions conducted by optogenetic proteins can result in cellular side effects. At the network level, activation or silencing of defined neural populations can alter the physiology of local or distant circuits, sometimes in undesired ways. We discuss how, in order to design interpretable behavioral experiments using optogenetics, one can understand, and control for, these potential confounds.National Institutes of Health (U.S.) (NIH Director’s Pioneer Award 1DP1NS087724)MIT Media Lab ConsortiumNational Institutes of Health (U.S.) (NIH grant 1R01DA029639)National Institutes of Health (U.S.) (NIH grant 2R44NS070453)Massachusetts Institute of Technology. Synthetic Intelligence Laborator
Genetically encoded molecular tools for light-driven silencing of targeted neurons [Chapter 3]
No full textThe ability to silence, in a temporally precise fashion, the electrical activity of specific neurons embedded within intact brain tissue, is important for understanding the role that those neurons play in behaviors, brain disorders, and neural computations. “Optogenetic” silencers, genetically encoded molecules that, when expressed in targeted cells within neural networks, enable their electrical activity to be quieted in response to pulses of light, are enabling these kinds of causal circuit analyses studies. Two major classes of optogenetic silencer are in broad use in species ranging from worm to monkey: light-driven inward chloride pumps, or halorhodopsins, and light-driven outward proton pumps, such as archaerhodopsins and fungal light-driven proton pumps. Both classes of molecule, when expressed in neurons via viral or other transgenic means, enable the targeted neurons to be hyperpolarized by light. We here review the current status of these sets of molecules, and discuss how they are being discovered and engineered. We also discuss their expression properties, ionic properties, spectral characteristics, and kinetics. Such tools may not only find many uses in the quieting of electrical activity for basic science studies but may also, in the future, find clinical uses for their ability to safely and transiently shut down cellular electrical activity in a precise fashion.National Institutes of Health (U.S.) (NIH Director’s Pioneer Award DP2OD002002)National Institutes of Health (U.S.) (NIH grant 1R01NS075421)National Institutes of Health (U.S.) (NIH grant 1R01DA029639)National Institutes of Health (U.S.) (NIH grant 1RC1MH088182)National Institutes of Health (U.S.) (NIH grant 1RC2DE020919)National Institutes of Health (U.S.) (NIH grant 1R01NS067199)National Institutes of Health (U.S.) (NIH grant 1R43NS070453)National Science Foundation (U.S.) (NSF Grant EFRI 0835878)National Science Foundation (U.S.) (NSF Grant DMS 0848804)National Science Foundation (U.S.) (NSF Grant DMS 1042134
Independent control of gamma and theta activity by distinct interneuron networks in the olfactory bulb
No full textCircuits in the brain possess the ability to orchestrate activities on different timescales, but the manner in which distinct circuits interact to sculpt diverse rhythms remains unresolved. The olfactory bulb is a classic example of a place in which slow theta and fast gamma rhythms coexist. Furthermore, inhibitory interneurons that are generally implicated in rhythm generation are segregated into distinct layers, neatly separating local and global motifs. We combined intracellular recordings in vivo with circuit-specific optogenetic interference to examine the contribution of inhibition to rhythmic activity in the mouse olfactory bulb. We found that the two inhibitory circuits controlled rhythms on distinct timescales: local, glomerular networks coordinated theta activity, regulating baseline and odor-evoked inhibition, whereas granule cells orchestrated gamma synchrony and spike timing. Notably, granule cells did not contribute to baseline rhythms or sniff-coupled odor-evoked inhibition. Thus, activities on theta and gamma timescales are controlled by separate, dissociable inhibitory networks in the olfactory bulb.Deutsche Forschungsgemeinschaft (DFG-SPP1392)Max Planck Society for the Advancement of ScienceAlexander von Humboldt-StiftungGermany. Federal Ministry of Education and Research (US-German collaboration computational neuroscience)Medical Research Council (Great Britain) (MC_UP_1202/5)University of Tubingen (ExcellenzCluster Cell Networks
Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant
No full textAvailable in PMC 2015 June 14Contemporary auditory brainstem implant (ABI) performance is limited by reliance on electrical neurostimulation with its accompanying channel cross talk and current spread to non-auditory neurons. A new generation ABI based on optogenetic technology may ameliorate limitations fundamental to electrical stimulation. The most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively slow kinetic properties may prevent the encoding of auditory information at high stimulation rates. In the present study, we compare the temporal resolution of light-evoked responses of ChR2 to a recently developed fast opsin, Chronos, to ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral craniotomy was used to express Chronos or ChR2 in the cochlear nucleus (CN). Following a four to eight week incubation period, blue light (473 nm) was delivered via an optical fiber placed directly on the surface of the infected CN, and neural activity was recorded in the contralateral inferior colliculus (IC). Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high pulse rates. In addition, optical stimulation evoked excitatory responses throughout the tonotopic axis of the IC. Synchrony of the light-evoked response to stimulus rates of 14–448 pulses/s was higher in Chronos compared to ChR2 mice (p < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate that Chronos has the ability to drive the auditory system at higher stimulation rates than ChR2 and may be a more ideal opsin for manipulation of auditory pathways in future optogenetic-based neuroprostheses
Multiwaveguide implantable probe for light delivery to sets of distributed brain targets
No full textOptical fibers are commonly inserted into living tissues such as the brain in order to deliver light to deep targets for neuroscientific and neuroengineering applications such as optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins. However, an optical fiber is limited to delivering light to a single target within the three-dimensional structure of the brain. We here demonstrate a multiwaveguide probe capable of independently delivering light to multiple targets along the probe axis, thus enabling versatile optical control of sets of distributed brain targets. The 1.45-cm-long probe is microfabricated in the form of a 360-μm-wide array of 12 parallel silicon oxynitride (SiON) multimode waveguides clad with SiO2 and coated with aluminum; probes of custom dimensions are easily created as well. The waveguide array accepts light from a set of sources at the input end and guides the light down each waveguide to an aluminum corner mirror that efficiently deflects light away from the probe axis. Light losses at each stage are small (input coupling loss, 0.4±0.3dB; bend loss, negligible; propagation loss, 3.1±1dB/cm using the outscattering method and 3.2±0.4dB/cm using the cutback method; corner mirror loss, 1.5±0.4dB); a waveguide coupled, for example, to a 5mW source will deliver over 1.5mW to a target at a depth of 1cm.National Science Foundation (U.S.)National Institutes of Health (U.S.)Paul G. Allen Family FoundationBrain and Behavior Research FoundationAlfred P. Sloan FoundationDr. Gerald Burnett and Marjorie BurnettWallace H. Coulter FoundationBenesse Foundatio
Drug discovery: A jump-start for electroceuticals
Full text linkImagine a day when electrical impulses are a mainstay of medical treatment. Your clinician will administer electroceuticals that target individual nerve fibres or specific brain circuits to treat an array of conditions. These will modulate the neural impulses that control the body, repair lost function and reinstate a healthy balance. They could coax insulin from islet cells, regulate food intake, and control inflammation. They may treat pressing major ailments such as hypertension, diabetes, obesity, heart failure, pulmonary and vascular disease. All this is within reach, we argue, if researchers from disparate disciplines in academia and industry work together. We herewith outline what needs to be done to bring about electroceuticals, and unveil a public-private research initiative and award that aim to catalyse the field
Close-Packed Silicon Microelectrodes for Scalable Spatially Oversampled Neural Recording
Full text linkObjective: Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are closely packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes to enable spatially oversampled recording of neural activity in a scalable fashion. Methods: Our probes are fabricated in a hybrid lithography process, resulting in a dense array of recording sites connected to submicron dimension wiring. Results: We demonstrate an implementation of a probe comprising 1000 electrode pads, each 9 × 9 μm, at a pitch of 11 μm. We introduce design automation and packaging methods that allow us to readily create a large variety of different designs. Significance: We perform neural recordings with such probes in the live mammalian brain that illustrate the spatial oversampling potential of closely packed electrode sites.Massachusetts Institute of Technology. Simons Center for the Social BrainNational Institutes of Health (U.S.) (NIH Director’s Pioneer Award DP1NS087724)National Institutes of Health (U.S.) (NIH Grant R01NS067199)National Institutes of Health (U.S.) (NIH grant Grant 2R44NS070453- 03A1)National Institutes of Health (U.S.) (NIH Grant R01DA029639)National Science Foundation (U.S.) (Cognitive Rhythms Collaborative, NSF DMS 1042134)Institution of Engineering and Technology (IET) (Harvey Prize)New York Stem Cell FoundationNational Institutes of Health (U.S.) (NIH grant CBET 1053233)United States. Defense Advanced Research Projects Agency (DARPA Grant HR0011-14-2-0004)Paul G. Allen Family Foundatio
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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