Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals.
GCaMP; channelrhodopsin; halorhodopsin; imaging; neurophysiology; optogenetics.
Optogenetics for control of genetically or topologically defined neural subtypes. (
a) Electrical stimulation can be effective for modulating local neural activity, but the heterogeneity of brain tissue precludes control of single cell types using this method ( left). Genetically targetable optogenetic constructs enable more precise stimulation of specified neural subtypes intermingled with nontargeted neurons ( right). (Panel modified with permission from 154.) ( b) Many different types of optogenetic constructs have been developed for control of neural activity. Currently available tools allow for induction of action potentials (ChR-family light-gated cation channels shown, left), silencing of neural activity (HR-family light-gated chloride pumps shown, middle; proton pumps may also be used), and modulation of intracellular signaling cascades [OptoXR family (153) shown, right; other classes of biochemical tool may also be used], among many other applications. (Panel modified with permission from 4.) Abbreviations: ChR, channelrhodopsin; ChR2, channelrhodopsin-2; HR, halorhodopsin; NpHR, halorhodopsin from Natronomonas pharaonis; optoXR, opsin-receptor chimaera.
Optical-neural interfaces for light delivery to brain tissue in freely moving mammals. (
a) The original fiberoptic neural interface (27a), in this case implemented via a cannula implanted over the brain region of interest; the optical fiber coupled to a light source is inserted during behavioral testing. This approach allows for simple integration with pharmacological methods. (Panel modified with permission from .) ( b) Light delivery through an implanted fiber. An optical fiber stub is implanted over the brain region of interest and is coupled to a fiberoptic tether with a ceramic sheath during behavior. This approach is well suited to high-throughput behavioral testing but cannot be easily combined with pharmacology at the same site. Both cannulas and optical fiber stubs can be used for single- or dual-site illumination. (Panel modified with permission from 29 and 154.) Further advancements include ( c) multisite light delivery (panel modified with permission from 42) and ( d) wireless control (panel modified with permission from 37), both appropriately sized for use in freely behaving mice. ( e) Injectable optoelectronics for wireless multisite multiwavelength optical stimulation/sensing, electrophysiology, and temperature sensing with coregistration and minimal tissue damage. Multiple μ-ILED light sources (a thousandth the size of conventional LEDs) can be independently controlled and can deliver a choice of wavelengths. Abbreviations: μ-IPD, microscale inorganic photodetector; μ-ILED, microscale inorganic light-emitting diode. (Panel modified with permission from 48.)
Integrated neurophysiology and optical control. (
a) Optical fibers can be incorporated into multisite silicon probe designs suitable for use in freely behaving rats. (Panel modified with permission from 58.) ( b) A tetrode microdrive with independently drivable tetrodes can be modified to incorporate either a fixed or freely movable optical fiber for use in large, superficial brain regions such as cortex or the hippocampus. (Panel modified with permission from 63.) ( c) Simultaneous optical stimulation and electrical recording from small, deep structures, such as the brainstem neuromodulatory nuclei, requires a more compact design. A drivable device achieves this with tetrodes attached to a central fiber core. (Panel modified with permission from 61.)( d) An optical fiber can replace an electrode on a multielectrode array to enable simultaneous optical stimulation and high-density cortical recording. (Panel modified with permission from 65.)
Optical-neural interfaces for readout of neural signals. Several approaches have been developed for optically monitoring neural signals in freely behaving mammals. (
a) Fiber-based bulk tissue optical recording. A single multimode optical fiber is implanted over a brain area of interest in order to record fluorescence signals from neurons expressing genetically encoded Ca 2+ or voltage indicators. This system is particularly suitable for use in freely behaving mice owing to the small form factor and minimal weight of the implanted fiber. (Panel modified with permission from 96.) ( b) One-photon imaging through a fiber bundle permits the construction of population-scale two-dimensional images, which can be used to monitor layer-specific neural activity. (Panel modified with permission from .)( c) Head-mounted two-photon microscopy suitable for imaging cellular-resolution cortical fluorescence signals in behaving rats (97). ( d) A lightweight one-photon endoscopic microscopy system that can be used to image cellular-resolution neural activity in deep structures in behaving mice. (Panel modified with permission from 101.) ( e) Ca 2+-imaging data collected with the system depicted in panel d. ( top) CA1 principal neurons identified by Ca 2+ imaging. ( bottom) Ca 2+ signals recorded from this neural population in a freely behaving mouse. (Panel modified with permission from 146.) Abbreviations: CMOS, complementary metal-oxide semiconductor; F, fluorescence; LED, light-emitting diode; OGB-1 AM, Oregon Green 488 BAPTA-1; PMT, photomultiplier tube; ROI, region of interest; TCSPC, time-correlated single-photon counting.
All-Optical Interrogation of Neural Circuits
V Emiliani et al.
J Neurosci 35 (41), 13917-26.
This review describes the nexus of dramatic recent developments in optogenetic probes, genetically encoded activity sensors, and novel microscopies, which together allow …
A Neurophotonic Device for Stimulation and Recording of Neural Microcircuits
J Wang et al.
Conf Proc IEEE Eng Med Biol Soc 2010, 2935-8.
Neural stimulation and recording with high spatiotemporal precision is desirable for studying the real time cellular basis of neural circuits, as well as developing possi …
High-density Optrodes for Multi-Scale Electrophysiology and Optogenetic Stimulation
M Chamanzar et al.
Conf Proc IEEE Eng Med Biol Soc 2014, 6838-41.
We demonstrate the design and implementation of hybrid optical-electrical probes (`optrodes') for high resolution electrophysiology and optogenetic stimulation of neurons …
Optical Developments for Optogenetics
Biol Cell 105 (10), 443-64.
Brain intricacies and the difficulty that scientists encounter in revealing its function with standard approaches such as electrical stimulation of neurons have led to th …
Making Sense of Optogenetics
A Guru et al.
Int J Neuropsychopharmacol 18 (11), pyv079.
This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically-def …
PubMed Central articles
Implantable Neural Probes for Brain-Machine Interfaces - Current Developments and Future Prospects
JR Choi et al.
Exp Neurobiol 27 (6), 453-471.
A Brain-Machine interface (BMI) allows for direct communication between the brain and machines. Neural probes for recording neural signals are among the essential compone …
Progress in Research of Flexible MEMS Microelectrodes for Neural Interface
LJ Tang et al.
Micromachines (Basel) 8 (9).
With the rapid development of Micro-electro-mechanical Systems (MEMS) fabrication technologies, many microelectrodes with various structures and functions have been desig …
Transient Magnetothermal Neuronal Silencing Using the Chloride Channel Anoctamin 1 (TMEM16A)
R Munshi et al.
Front Neurosci 12, 560.
Determining the role and necessity of specific neurons in a network calls for precisely timed, reversible removal of these neurons from the circuit via remotely triggered …
High-density Microfibers as a Potential Optical Interface to Reach Deep Brain Regions
LN Perkins et al.
J Neural Eng 15 (6), 066002.
At a depth of 3 mm, histology shows fibers consistently splay over 1 mm in diameter throughout the target region. Immunohistochemical staining after chronic implants reve …
Biocompatible and Implantable Optical Fibers and Waveguides for Biomedicine
R Nazempour et al.
Materials (Basel) 11 (8).
Optical fibers and waveguides in general effectively control and modulate light propagation, and these tools have been extensively used in communication, lighting and sen …
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