Next-generation interfaces for studying neural function

Monitoring and modulating the diversity of signals used by neurons and glia in a closed-loop fashion is necessary to establish causative links between biochemical processes within the nervous system and observed behaviors. As developments in neural-interface hardware strive to keep pace with rapid progress in genetically encoded and synthetic reporters and modulators of neural activity, the integration of multiple functional features becomes a key requirement and a pressing challenge in the field of neural engineering. Electrical, optical and chemical approaches have been used to manipulate and record neuronal activity in vivo, with a recent focus on technologies that both integrate multiple modes of interaction with neurons into a single device and enable bidirectional communication with neural circuits with enhanced spatiotemporal precision. These technologies not only are facilitating a greater understanding of the brain, spinal cord and peripheral circuits in the context of health and disease, but also are informing the development of future closed-loop therapies for neurological, neuro-immune and neuroendocrine conditions. Anikeeva and colleagues review the state of the art in technologies that enable discoveries of brain function and the development of novel therapeutic approaches.

[1]  G. Buzsáki,et al.  Fiberless multicolor neural optoelectrode for in vivo circuit analysis , 2016, Scientific Reports.

[2]  Christina M. Tringides,et al.  Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo , 2015, Nature Biotechnology.

[3]  Thomas J. Richner,et al.  Flexible and stretchable nanowire-coated fibers for optoelectronic probing of spinal cord circuits , 2017, Science Advances.

[4]  John A Rogers,et al.  Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain , 2018, Proceedings of the National Academy of Sciences.

[5]  G. Buzsáki,et al.  Monolithically Integrated μLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals , 2015, Neuron.

[6]  Michelle L Rogers,et al.  Simultaneous monitoring of potassium, glucose and lactate during spreading depolarization in the injured human brain – Proof of principle of a novel real-time neurochemical analysis system, continuous online microdialysis , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  Michael Z. Lin,et al.  Genetically encoded indicators of neuronal activity , 2016, Nature Neuroscience.

[8]  György Buzsáki,et al.  High-Density Stretchable Electrode Grids for Chronic Neural Recording , 2018, Advanced materials.

[9]  Craig T. Nordhausen,et al.  Single unit recording capabilities of a 100 microelectrode array , 1996, Brain Research.

[10]  L. Sombers,et al.  Fast-Scan Cyclic Voltammetry: Chemical Sensing in the Brain and Beyond. , 2018, Analytical chemistry.

[11]  Francois Pomerleau,et al.  Ceramic-based multisite microelectrode arrays for simultaneous measures of choline and acetylcholine in CNS. , 2008, Biosensors & bioelectronics.

[12]  Raag D. Airan,et al.  Natural Neural Projection Dynamics Underlying Social Behavior , 2014, Cell.

[13]  G. Gerhardt,et al.  Microelectrode array studies of basal and potassium‐evoked release of l‐glutamate in the anesthetized rat brain , 2006, Journal of neurochemistry.

[14]  Chin-Tu Chen,et al.  Rational design of silicon structures for optically controlled multiscale biointerfaces , 2018, Nature Biomedical Engineering.

[15]  Takao Someya,et al.  Transparent, conformable, active multielectrode array using organic electrochemical transistors , 2017, Proceedings of the National Academy of Sciences.

[16]  Justin A. Johnson,et al.  Failure of Standard Training Sets in the Analysis of Fast-Scan Cyclic Voltammetry Data. , 2016, ACS chemical neuroscience.

[17]  I. Ozden,et al.  Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording , 2015, Nature Methods.

[18]  K. Deisseroth,et al.  Optogenetic stimulation of a hippocampal engram activates fear memory recall , 2012, Nature.

[19]  T. S. White,et al.  Microfabricated Probes for Studying Brain Chemistry: A Review. , 2018, Chemphyschem : a European journal of chemical physics and physical chemistry.

[20]  J. Simon Wiegert,et al.  Anion-conducting channelrhodopsins with tuned spectra and modified kinetics engineered for optogenetic manipulation of behavior , 2017, bioRxiv.

[21]  Dirk Trauner,et al.  In Vivo Photopharmacology. , 2018, Chemical reviews.

[22]  J. Joannopoulos,et al.  Thermally-drawn fibers with spatially-selective porous domains , 2017, Nature Communications.

[23]  Il-Joo Cho,et al.  Neural probes with multi-drug delivery capability. , 2015, Lab on a chip.

[24]  Robert Langer,et al.  Miniaturized neural system for chronic, local intracerebral drug delivery , 2018, Science Translational Medicine.

[25]  R. Mark Wightman,et al.  An implantable multimodal sensor for oxygen, neurotransmitters, and electrophysiology during spreading depolarization in the deep brain. , 2017, The Analyst.

[26]  Christopher J. Tassone,et al.  Structural control of mixed ionic and electronic transport in conducting polymers , 2016, Nature Communications.

[27]  Tao Zhou,et al.  Stable long-term chronic brain mapping at the single-neuron level , 2016, Nature Methods.

[28]  T. Lucas,et al.  Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging , 2014, Nature Communications.

[29]  Anatol C. Kreitzer,et al.  A Genetically Encoded Fluorescent Sensor Enables Rapid and Specific Detection of Dopamine in Flies, Fish, and Mice , 2018, Cell.

[30]  B. Zemelman,et al.  Selective Photostimulation of Genetically ChARGed Neurons , 2002, Neuron.

[31]  S. Cooper,et al.  Remote Control , 2002, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[32]  S. Ferré,et al.  Local Control of Extracellular Dopamine Levels in the Medial Nucleus Accumbens by a Glutamatergic Projection from the Infralimbic Cortex , 2016, The Journal of Neuroscience.

[33]  Takashi Kawashima,et al.  A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters , 2017, Nature Chemical Biology.

[34]  Xi-Ping Huang,et al.  A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior , 2015, Neuron.

[35]  René M Rossi,et al.  Superelastic Multimaterial Electronic and Photonic Fibers and Devices via Thermal Drawing , 2018, Advanced materials.

[36]  Anna Devor,et al.  Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays , 2018, Nature Communications.

[37]  B. Roska,et al.  Virus stamping for targeted single-cell infection in vitro and in vivo , 2017, Nature Biotechnology.

[38]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[39]  B. Zoltowski,et al.  Optimized second generation CRY2/CIB dimerizers and photoactivatable Cre recombinase , 2016, Nature chemical biology.

[40]  L. Sombers,et al.  Selective and Mechanically Robust Sensors for Electrochemical Measurements of Real-Time Hydrogen Peroxide Dynamics in Vivo. , 2018, Analytical chemistry.

[41]  Carsten Schultz,et al.  Recent developments of genetically encoded optical sensors for cell biology , 2017, Biology of the cell.

[42]  Bernardo L. Sabatini,et al.  Silk Fibroin Films Facilitate Single-Step Targeted Expression of Optogenetic Proteins , 2018, Cell reports.

[43]  M. Nicolelis,et al.  Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G Protein-Coupled Receptors , 2009, Neuron.

[44]  A. Gamal,et al.  Miniaturized integration of a fluorescence microscope , 2011, Nature Methods.

[45]  Zhenqiang Ma,et al.  Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice. , 2018, ACS nano.

[46]  Robert Langer,et al.  Long-term dopamine neurochemical monitoring in primates , 2017, Proceedings of the National Academy of Sciences.

[47]  Talia N. Lerner,et al.  Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain , 2016, Nature Methods.

[48]  Iain McCulloch,et al.  Conjugated Polymers in Bioelectronics. , 2018, Accounts of chemical research.

[49]  Sergey L. Gratiy,et al.  Fully integrated silicon probes for high-density recording of neural activity , 2017, Nature.

[50]  Mohamady El-Gaby,et al.  Archaerhodopsin Selectively and Reversibly Silences Synaptic Transmission through Altered pH , 2016, Cell reports.

[51]  O. Mabrouk,et al.  Benzoyl chloride derivatization with liquid chromatography-mass spectrometry for targeted metabolomics of neurochemicals in biological samples. , 2016, Journal of chromatography. A.

[52]  X. Jia,et al.  One-Step Optogenetics with Multifunctional Flexible Polymer Fibers , 2017, Nature Neuroscience.

[53]  Stephen J. Capuzzi,et al.  Design and Profiling of a Subcellular Targeted Optogenetic cAMP-Dependent Protein Kinase. , 2017, Cell chemical biology.

[54]  G. Buzsáki,et al.  NeuroGrid: recording action potentials from the surface of the brain , 2014, Nature Neuroscience.

[55]  Yevgenia Kozorovitskiy,et al.  Photoactivatable drugs for nicotinic optopharmacology , 2018, Nature Methods.

[56]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[57]  G. Nagel,et al.  Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain , 2018, Nature Communications.

[58]  L. Reymond,et al.  Genetic targeting of chemical indicators in vivo , 2014, Nature Methods.

[59]  K. Tye,et al.  A light- and calcium-gated transcription factor for imaging and manipulating activated neurons , 2017, Nature Biotechnology.

[60]  Xinyan Tracy Cui,et al.  Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes. , 2017, Biosensors & bioelectronics.

[61]  Nephi Stella,et al.  Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals , 2009, Nature Methods.

[62]  Jordan G McCall,et al.  In vivo detection of optically-evoked opioid peptide release , 2018, bioRxiv.

[63]  George G. Malliaras,et al.  A Microfluidic Ion Pump for In Vivo Drug Delivery , 2017, Advanced materials.

[64]  C. Mulle,et al.  Exclusive photorelease of signalling lipids at the plasma membrane , 2015, Nature Communications.

[65]  Elmira Anderzhanova,et al.  Brain microdialysis and its applications in experimental neurochemistry , 2013, Cell and Tissue Research.

[66]  J. Y. Sim,et al.  Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics , 2015, Cell.

[67]  Laurie D. Burns,et al.  High-speed, miniaturized fluorescence microscopy in freely moving mice , 2008, Nature Methods.

[68]  S. Samanta,et al.  Red-Shifting Azobenzene Photoswitches for in Vivo Use. , 2015, Accounts of chemical research.

[69]  Mohamed S. Emara,et al.  Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber , 2017, Nature Neuroscience.

[70]  Benjamin C. Johnson,et al.  Toward true closed-loop neuromodulation: artifact-free recording during stimulation , 2018, Current Opinion in Neurobiology.

[71]  Kai Bodensiek,et al.  High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics , 2018, Nature Communications.

[72]  Polina Anikeeva,et al.  Neural Recording and Modulation Technologies. , 2017, Nature reviews. Materials.

[73]  Nathan C. Klapoetke,et al.  Sub-millisecond optogenetic control of neuronal firing with two-photon holographic photoactivation of Chronos , 2016, bioRxiv.

[74]  Heping Cheng,et al.  Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice , 2017, Nature Methods.

[75]  David Fitzpatrick,et al.  Stability, affinity and chromatic variants of the glutamate sensor iGluSnFR , 2018, Nature Methods.

[76]  Emmanuel M. Drakakis,et al.  High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring , 2016, Front. Hum. Neurosci..

[77]  Karl Deisseroth,et al.  The form and function of channelrhodopsin , 2017, Science.

[78]  N. Bursac,et al.  Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells , 2017, Theranostics.

[79]  Xue Li,et al.  Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes. , 2017, Nano letters.

[80]  T. Hamakubo,et al.  Optical inactivation of synaptic AMPA receptors erases fear memory , 2016, Nature Biotechnology.

[81]  Bert Sakmann,et al.  Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator , 2015, Proceedings of the National Academy of Sciences.

[82]  A. Nimmerjahn,et al.  Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors , 2018, Science.

[83]  Jessica A. Cardin,et al.  Noninvasive optical inhibition with a red-shifted microbial rhodopsin , 2014, Nature Neuroscience.

[84]  Yoel Fink,et al.  Diode fibres for fabric-based optical communications , 2018, Nature.

[85]  R. Wightman,et al.  Monitoring rapid chemical communication in the brain. , 2008, Chemical reviews.

[86]  H. Berger,et al.  Über das Elektrenkephalogramm des Menschen , 1937, Archiv für Psychiatrie und Nervenkrankheiten.

[87]  Vaughn L. Hetrick,et al.  Mesolimbic Dopamine Signals the Value of Work , 2015, Nature Neuroscience.

[88]  Evan W. Miller,et al.  Isomerically Pure Tetramethylrhodamine Voltage Reporters. , 2016, Journal of the American Chemical Society.

[89]  Huanan Zhang,et al.  Chronic in vivo stability assessment of carbon fiber microelectrode arrays , 2016, Journal of neural engineering.

[90]  L. Sombers,et al.  Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum. , 2017, ACS chemical neuroscience.

[91]  L. Reymond,et al.  Semisynthetic biosensors for mapping cellular concentrations of nicotinamide adenine dinucleotides , 2018, eLife.

[92]  Arnaud Bertsch,et al.  Neural probe combining microelectrodes and a droplet-based microdialysis collection system for high temporal resolution sampling. , 2016, Lab on a chip.

[93]  G. Gerhardt,et al.  L-lactate measures in brain tissue with ceramic-based multisite microelectrodes. , 2005, Biosensors & bioelectronics.

[94]  G. Buzsáki,et al.  Dual color optogenetic control of neural populations using low-noise, multishank optoelectrodes , 2018, Microsystems & Nanoengineering.

[95]  Duygu Kuzum,et al.  Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing , 2016, Scientific Reports.

[96]  Nathan T. Rodeberg,et al.  Construction of Training Sets for Valid Calibration of in Vivo Cyclic Voltammetric Data by Principal Component Analysis. , 2015, Analytical chemistry.

[97]  K. Deisseroth,et al.  Targeting Neural Circuits , 2016, Cell.

[98]  Shai Berlin,et al.  Photoactivatable Genetically-Encoded Calcium Indicators for targeted neuronal imaging , 2015, Nature Methods.

[99]  D. Perrais,et al.  Semisynthetic fluorescent pH sensors for imaging exocytosis and endocytosis , 2017, Nature Communications.

[100]  Robert T Kennedy,et al.  Improved temporal resolution for in vivo microdialysis by using segmented flow. , 2008, Analytical chemistry.

[101]  Dongmin Lee,et al.  A calcium- and light-gated switch to induce gene expression in activated neurons , 2017, Nature Biotechnology.

[102]  Etienne E. Pracht,et al.  The burden of neurological disease in the United States: A summary report and call to action , 2017, Annals of neurology.

[103]  Hoon-Ki Min,et al.  A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain , 2016, Front. Hum. Neurosci..

[104]  Patrick A Tresco,et al.  BBB leakage, astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance. , 2015, Biomaterials.

[105]  Hongkui Zeng,et al.  Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse , 2016, The Journal of Neuroscience.

[106]  Emiliano Ronzitti,et al.  Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos , 2016, The Journal of Neuroscience.

[107]  Silvestro Micera,et al.  Electronic dura mater for long-term multimodal neural interfaces , 2015, Science.

[108]  Tomáš Čižmár,et al.  High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging , 2018, Light: Science & Applications.

[109]  Christian Henneberger,et al.  Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS , 2018, Nature Chemical Biology.

[110]  Ji Woong Yu,et al.  Highly conductive, stretchable and biocompatible Ag–Au core–sheath nanowire composite for wearable and implantable bioelectronics , 2018, Nature Nanotechnology.

[111]  E. Boyden,et al.  Temporally precise single-cell resolution optogenetics , 2017, Nature Neuroscience.

[112]  Huanan Zhang,et al.  Insertion of linear 8.4 μm diameter 16 channel carbon fiber electrode arrays for single unit recordings , 2015, Journal of neural engineering.

[113]  William E. Allen,et al.  Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex , 2017, Neuron.

[114]  P. Hegemann,et al.  Electrical properties, substrate specificity and optogenetic potential of the engineered light-driven sodium pump eKR2 , 2018, Scientific Reports.

[115]  Jing Wang,et al.  Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications , 2012, Journal of neural engineering.

[116]  Hyeun Joong Yoon,et al.  Microfabrication and in Vivo Performance of a Microdialysis Probe with Embedded Membrane. , 2016, Analytical chemistry.

[117]  Brenda C. Shields,et al.  Deconstructing behavioral neuropharmacology with cellular specificity , 2017, Science.

[118]  Kira E. Poskanzer,et al.  Optical Probes for Neurobiological Sensing and Imaging. , 2018, Accounts of chemical research.

[119]  Nathan T. Rodeberg,et al.  Hitchhiker's Guide to Voltammetry: Acute and Chronic Electrodes for in Vivo Fast-Scan Cyclic Voltammetry , 2017, ACS chemical neuroscience.

[120]  Li I. Zhang,et al.  ED SUM: Signaling by the neurotransmitter acetylcholine is monitored in cells and animals with a sensitive reporter. , 2018, Nature Biotechnology.

[121]  O. Yizhar,et al.  Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins , 2017, Proceedings of the National Academy of Sciences.

[122]  Dirk Trauner,et al.  Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor , 2017, Nature Communications.

[123]  Michael Z. Lin,et al.  Cell-Type-Specific Optical Recording of Membrane Voltage Dynamics in Freely Moving Mice , 2016, Cell.

[124]  K. Horch,et al.  A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array , 1991, IEEE Transactions on Biomedical Engineering.

[125]  Yuji Ikegaya,et al.  Genetically Encoded Green Fluorescent Ca2+ Indicators with Improved Detectability for Neuronal Ca2+ Signals , 2012, PloS one.

[126]  André Nadler,et al.  A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers , 2018, Angewandte Chemie.

[127]  Dietmar Schmitz,et al.  Optogenetic Tools for Subcellular Applications in Neuroscience , 2017, Neuron.

[128]  Thomas J. Jentsch,et al.  Optogenetic Acidification of Synaptic Vesicles and Lysosomes , 2015, Nature Neuroscience.

[129]  Karl Deisseroth,et al.  Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system , 2016, Science Translational Medicine.

[130]  A. Gordus,et al.  Sensitive red protein calcium indicators for imaging neural activity , 2016, bioRxiv.

[131]  Xiao Yang,et al.  A method for single-neuron chronic recording from the retina in awake mice , 2018, Science.

[132]  M. Ward,et al.  Toward a comparison of microelectrodes for acute and chronic recordings , 2009, Brain Research.

[133]  U. Egert,et al.  Optogenetic entrainment of neural oscillations with hybrid fiber probes , 2018, Journal of neural engineering.

[134]  V. Gradinaru,et al.  Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems , 2017, Nature Neuroscience.

[135]  K. Tye,et al.  Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex , 2016, Neuroscience.

[136]  L. Sombers,et al.  Enzyme-modified carbon-fiber microelectrode for the quantification of dynamic fluctuations of nonelectroactive analytes using fast-scan cyclic voltammetry. , 2013, Analytical chemistry.

[137]  R. Kennedy,et al.  Microdialysis Coupled with LC-MS/MS for In Vivo Neurochemical Monitoring , 2017, The AAPS Journal.

[138]  Dirk Trauner,et al.  Dual optical control and mechanistic insights into photoswitchable group II and III metabotropic glutamate receptors , 2017, Proceedings of the National Academy of Sciences.

[139]  D. Trauner,et al.  A roadmap to success in photopharmacology. , 2015, Accounts of Chemical Research.

[140]  K. Deisseroth,et al.  Neural substrates of awakening probed with optogenetic control of hypocretin neurons , 2007, Nature.