Preparation and implementation of optofluidic neural probes for in vivo wireless pharmacology and optogenetics

This Protocol Extension describes the fabrication and technical procedures for implementing ultrathin, flexible optofluidic neural probe systems that provide targeted, wireless delivery of fluids and light into the brains of awake, freely behaving animals. As a Protocol Extension article, this article describes an adaptation of an existing Protocol that offers additional applications. This protocol serves as an extension of an existing Nature Protocol describing optoelectronic devices for studying intact neural systems. Here, we describe additional features of fabricating self-contained platforms that involve flexible microfluidic probes, pumping systems, microscale inorganic LEDs, wireless-control electronics, and power supplies. These small, flexible probes minimize tissue damage and inflammation, making long-term implantation possible. The capabilities include wireless pharmacological and optical intervention for dissecting neural circuitry during behavior. The fabrication can be completed in 1–2 weeks, and the devices can be used for 1–2 weeks of in vivo rodent experiments. To successfully carry out the protocol, researchers should have basic skill sets in photolithography and soft lithography, as well as experience with stereotaxic surgery and behavioral neuroscience practices. These fabrication processes and implementation protocols will increase access to wireless optofluidic neural probes for advanced in vivo pharmacology and optogenetics in freely moving rodents.This protocol is an extension to: Nat. Protoc. 8, 2413–2428 (2013); doi:10.1038/nprot.2013.158; published online 07 November 2013

[1]  Peter A. Groblewski,et al.  Drug-induced conditioned place preference and aversion in mice , 2006, Nature Protocols.

[2]  A. Höke,et al.  Advances in peripheral nerve regeneration , 2013, Nature Reviews Neurology.

[3]  Bernardo L. Sabatini,et al.  Photoactivatable Neuropeptides for Spatiotemporally Precise Delivery of Opioids in Neural Tissue , 2012, Neuron.

[4]  Jordan G. McCall,et al.  Basolateral amygdala opioids contribute to increased high-fat intake following intra-accumbens opioid administration, but not following 24-h food deprivation , 2010, Pharmacology Biochemistry and Behavior.

[5]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[6]  John A Rogers,et al.  Ultraminiaturized photovoltaic and radio frequency powered optoelectronic systems for wireless optogenetics , 2015, Journal of neural engineering.

[7]  Roland Zengerle,et al.  An intra-cerebral drug delivery system for freely moving animals , 2012, Biomedical microdevices.

[8]  Jae-Woong Jeong,et al.  Soft Materials in Neuroengineering for Hard Problems in Neuroscience , 2015, Neuron.

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

[10]  E. Isacoff,et al.  Light-activated ion channels for remote control of neuronal firing , 2004, Nature Neuroscience.

[11]  Alex Rodriguez,et al.  A wirelessly powered and controlled device for optical neural control of freely-behaving animals , 2011, Journal of neural engineering.

[12]  K. L. Montgomery,et al.  Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice , 2015, Nature Methods.

[13]  Steven S. Vogel,et al.  Deep brain optical measurements of cell type–specific neural activity in behaving mice , 2014, Nature Protocols.

[14]  A. Douar,et al.  Current issues in adeno-associated viral vector production , 2005, Gene Therapy.

[15]  Jessica A. Cardin,et al.  Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2 , 2010, Nature Protocols.

[16]  Raag D. Airan,et al.  Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures , 2010, Nature Protocols.

[17]  B. Carter,et al.  Adenovirus helper function for growth of adeno-associated virus: effect of temperature-sensitive mutations in adenovirus early gene region 2 , 1980, Journal of virology.

[18]  Huanyu Cheng,et al.  A Physically Transient Form of Silicon Electronics , 2012, Science.

[19]  Edward S Boyden,et al.  Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits. , 2012, Optics letters.

[20]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[21]  Robert Langer,et al.  First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip , 2012, Science Translational Medicine.

[22]  Samuel C Funderburk,et al.  Spatiotemporal Control of Opioid Signaling and Behavior , 2015, Neuron.

[23]  G. Feng,et al.  Acute brain slice methods for adult and aging animals: application of targeted patch clamp analysis and optogenetics. , 2014, Methods in molecular biology.

[24]  Dirk Trauner,et al.  Photochemical Restoration of Visual Responses in Blind Mice , 2012, Neuron.

[25]  Michael C. McAlpine,et al.  Silk‐Based Conformal, Adhesive, Edible Food Sensors , 2012, Advanced materials.

[26]  Benjamin R. Arenkiel,et al.  In Vivo Light-Induced Activation of Neural Circuitry in Transgenic Mice Expressing Channelrhodopsin-2 , 2007, Neuron.

[27]  P. Sinn,et al.  Gene Therapy Progress and Prospects: Development of improved lentiviral and retroviral vectors – design, biosafety, and production , 2005, Gene Therapy.

[28]  Pedro P. Irazoqui,et al.  A Miniature, Fiber-Coupled, Wireless, Deep-Brain Optogenetic Stimulator , 2015, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

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

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

[31]  Katja Müller,et al.  The temperature stability of mouse retroviruses depends on the cholesterol levels of viral lipid shell and cellular plasma membrane. , 2003, Virology.

[32]  James M. Otis,et al.  Visualization of cortical, subcortical and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses , 2016, Nature Protocols.

[33]  B. Roth,et al.  Chemogenetic tools to interrogate brain functions. , 2014, Annual review of neuroscience.

[34]  John A Rogers,et al.  Fabrication and application of flexible, multimodal light-emitting devices for wireless optogenetics , 2013, Nature Protocols.

[35]  Anirvan Ghosh,et al.  Chemogenetic Synaptic Silencing of Neural Circuits Localizes a Hypothalamus→Midbrain Pathway for Feeding Behavior , 2014, Neuron.

[36]  G Petr,et al.  The effect of temperature on the hemagglutinin activity of the canine adenovirus (infectious canine hepatitis virus). , 2010, Zentralblatt fur Veterinarmedizin. Reihe B. Journal of veterinary medicine. Series B.

[37]  Mark A. Rossi,et al.  A wirelessly controlled implantable LED system for deep brain optogenetic stimulation , 2015, Front. Integr. Neurosci..

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

[39]  G Boschi,et al.  Implantation of an intracerebral cannula in the mouse. , 1981, Journal of pharmacological methods.

[40]  Justin A. Blanco,et al.  Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. , 2010, Nature materials.

[41]  W S Croughan,et al.  Comparative study of inactivation of herpes simplex virus types 1 and 2 by commonly used antiseptic agents , 1988, Journal of clinical microbiology.

[42]  Robert Langer,et al.  Magnetically triggered nanocomposite membranes: a versatile platform for triggered drug release. , 2011, Nano letters.

[43]  Benoit Gosselin,et al.  A wireless and batteryless neural headstage with optical stimulation and electrophysiological recording , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

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

[45]  Randall J. Platt,et al.  Optical Control of Mammalian Endogenous Transcription and Epigenetic States , 2013, Nature.

[46]  A. Cressant,et al.  Computerized video analysis of social interactions in mice , 2012, Nature Methods.

[47]  John A Rogers,et al.  Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics , 2015, Nature Biotechnology.

[48]  L P Noldus,et al.  EthoVision: A versatile video tracking system for automation of behavioral experiments , 2001, Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc.

[49]  A. Kawai,et al.  Temperature-sensitivity of the replication of rabies virus (HEP-flury strain) in BHK-21 cells. I. Alteration of viral RNA synthesis at the elevated temperature. , 1992, Virology.

[50]  J. McCall,et al.  CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety , 2015, Neuron.

[51]  J. A. Rogers,et al.  Soft microfluidic neural probes for wireless drug delivery in freely behaving mice , 2015, 2015 Transducers - 2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS).

[52]  Dirk Trauner,et al.  Restoring Visual Function to Blind Mice with a Photoswitch that Exploits Electrophysiological Remodeling of Retinal Ganglion Cells , 2014, Neuron.

[53]  Jin-Moo Lee,et al.  Photo-activatable Cre recombinase regulates gene expression in vivo , 2015, Scientific Reports.

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

[55]  Benjamin R. Arenkiel,et al.  Transient activation of specific neurons in mice by selective expression of the capsaicin receptor , 2012, Nature Communications.

[56]  K. Mathieson,et al.  Optogenetic activation of neocortical neurons in vivo with a sapphire-based micro-scale LED probe , 2015, Front. Neural Circuits.

[57]  A. Walf,et al.  The use of the elevated plus maze as an assay of anxiety-related behavior in rodents , 2007, Nature Protocols.

[58]  V. Chefer,et al.  Overview of Brain Microdialysis , 2009, Current protocols in neuroscience.

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

[60]  Garret D Stuber,et al.  Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits , 2011, Nature Protocols.

[61]  S. McMahon,et al.  Targeting novel peripheral mediators for the treatment of chronic pain. , 2013, British journal of anaesthesia.

[62]  A. Zorzos,et al.  Multiwaveguide implantable probe for light delivery to sets of distributed brain targets. , 2010, Optics letters.

[63]  Marzia Martina,et al.  Patch-Clamp Methods and Protocols , 2014, Methods in Molecular Biology.

[64]  Hajime Hirase,et al.  A simple head-mountable LED device for chronic stimulation of optogenetic molecules in freely moving mice , 2011, Neuroscience Research.

[65]  Richard Apps,et al.  A light microscope-based double retrograde tracer strategy to chart central neuronal connections , 2007, Nature Protocols.

[66]  B. Zemelman,et al.  Photochemical gating of heterologous ion channels: Remote control over genetically designated populations of neurons , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[67]  H. Adesnik,et al.  Optogenetic pharmacology for control of native neuronal signaling proteins , 2013, Nature Neuroscience.

[68]  W. Carlezon,et al.  Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation , 2007, Nature Protocols.

[69]  K. Deisseroth,et al.  Optogenetic investigation of neural circuits underlying brain disease in animal models , 2012, Nature Reviews Neuroscience.

[70]  J. Rogers,et al.  Optodynamic simulation of β-adrenergic receptor signalling , 2015, Nature Communications.

[71]  Nicole A. Crowley,et al.  Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward , 2015, Neuron.

[72]  Robert Langer,et al.  Near-infrared–actuated devices for remotely controlled drug delivery , 2014, Proceedings of the National Academy of Sciences.

[73]  Pavel Osten,et al.  Stereotaxic gene delivery in the rodent brain , 2007, Nature Protocols.

[74]  Robert Langer,et al.  A magnetically triggered composite membrane for on-demand drug delivery. , 2009, Nano letters.

[75]  Susana Q. Lima,et al.  Remote Control of Behavior through Genetically Targeted Photostimulation of Neurons , 2005, Cell.

[76]  R. Reep,et al.  Multiple neuroanatomical tract-tracing using fluorescent Alexa Fluor conjugates of cholera toxin subunit B in rats , 2009, Nature Protocols.

[77]  B. Roth,et al.  Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand , 2007, Proceedings of the National Academy of Sciences.