Optogenetic Modulation Research Articles

Optogenetics 2.0: challenges and solutions towards a quantitative probing of neural circuits.

To exploit the full potential of optogenetics, we need to titrate and tailor optogenetic methods to emulate naturalistic circuit function. For that, the following prerequisites need to be met: first, we need to target opsin expression not only to genetically defined neurons per se, but to specifically target a functional node. Second, we need to assess the scope of optogenetic modulation, i.e.the fraction of optogenetically modulated neurons. Third, we need to integrate optogenetic control in a closed loop setting. Fourth, we need to further safe and stable gene expression and light delivery to bring optogenetics to the clinics. Here, we review these concepts for the human and rodent brain.

Optogenetic Modulation of Arrhythmia Triggers: Proof-of-Concept from Computational Modeling.

Early afterdepolarizations (EADs) are secondary voltage depolarizations associated with reduced repolarization reserve (RRR) that can trigger lethal arrhythmias. Relating EADs to triggered activity is difficult to study, so the ability to suppress or provoke EADs would be experimentally useful. Here, we use computational simulations to assess the feasibility of subthreshold optogenetic stimulation modulating the propensity for EADs (cell-scale) and EAD-associated ectopic beats (organ-scale). We modified a ventricular ionic model by reducing rapid delayed rectifier potassium (0.25-0.1 × baseline) and increasing L-type calcium (1.0-3.5 × baseline) currents to create RRR conditions with varying severity. We ran simulations in models of single cardiomyocytes and left ventricles from post-myocardial infarction patient MRI scans. Optogenetic stimulation was simulated using either ChR2 (depolarizing) or GtACR1 (repolarizing) opsins. In cell-scale simulations without illumination, EADs were seen for 164 of 416 RRR conditions. Subthreshold stimulation of GtACR1 reduced EAD incidence by up to 84.8% (25/416 RRR conditions; 0.1μW/mm2); in contrast, subthreshold ChR2 excitation increased EAD incidence by up to 136.6% (388/416 RRR conditions; 50μW/mm2). At the organ scale, we assumed simultaneous, uniform illumination of the epicardial and endocardial surfaces. GtACR1-mediated suppression (10-50μW/mm2) and ChR2-mediated unmasking (50-100μW/mm2) of EAD-associated ectopic beats were feasible in three distinct ventricular models. Our findings suggest that optogenetics could be used to silence or provoke both EADs and EAD-associated ectopic beats. Validation in animal models could lead to exciting new experimental regimes and potentially to novel anti-arrhythmia treatments. The online version contains supplementary material available at 10.1007/s12195-023-00781-z.

Substantia Nigra Pars Reticulata Projections to the Pedunculopontine Nucleus Modulate Dyskinesia.

Long-term use of levodopa for Parkinson's disease (PD) treatment is often hindered by development of motor complications, including levodopa-induced dyskinesia (LID). The substantia nigra pars reticulata (SNr) and globus pallidus internal segment (GPi) are the output nuclei of the basal ganglia. Dysregulation of SNr and GPi activity contributes to PD pathophysiology and LID. The objective of this study was to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the pedunculopontine nucleus (PPN) regulates PD symptoms and LID in a mouse model. We expressed Cre-recombinase activated channelrhodopsin-2 (ChR2) or halorhodopsin adeno-associated virus-2 (AAV2) vectors selectively in SNr GABAergic neurons of Vgat-IRES-Cre mice in a 6-hydroxydopamine model of PD to investigate whether direct optogenetic modulation of SNr neurons or their projections to the PPN regulates PD symptoms and LID expression. The forepaw stepping task, mouse LID rating scale, and open-field locomotion were used to assess akinesia and LID to test the effect of SNr modulation. Akinesia was improved by suppressing SNr neuron activity with halorhodopsin. LID was significantly reduced by increasing SNr neuronal activity with ChR2, which did not interfere with the antiakinetic effect of levodopa. Optical stimulation of ChR2 in SNr projections to the PPN recapitulated direct SNr stimulation. Modulation of SNr GABAergic neurons alters akinesia and LID expression in a manner consistent with the rate model of basal ganglia circuitry. Moreover, the projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity, identifying a potential novel role for the PPN in LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Optogenetic modulation of guanine nucleotide exchange factors of Ras superfamily proteins directly controls cell shape and movement.

In this article, we provide detailed protocols on using optogenetic dimerizers to acutely perturb activities of guanine nucleotide exchange factors (GEFs) specific to Ras, Rac or Rho small GTPases of the migratory networks in various mammalian and amoeba cell lines. These GEFs are crucial components of signal transduction networks which link upstream G-protein coupled receptors to downstream cytoskeletal components and help cells migrate through their dynamic microenvironment. Conventional approaches to perturb and examine these signaling and cytoskeletal networks, such as gene knockout or overexpression, are protracted which allows networks to readjust through gene expression changes. Moreover, these tools lack spatial resolution to probe the effects of local network activations. To overcome these challenges, blue light-inducible cryptochrome- and LOV domain-based dimerization systems have been recently developed to control signaling or cytoskeletal events in a spatiotemporally precise manner. We illustrate that, within minutes of global membrane recruitment of full-length GEFs or their catalytic domains only, widespread increases or decreases in F-actin rich protrusions and cell size occur, depending on the particular node in the networks targeted. Additionally, we demonstrate localized GEF recruitment as a robust assay system to study local network activation-driven changes in polarity and directed migration. Altogether, these optical tools confirmed GEFs of Ras superfamily GTPases as regulators of cell shape, actin dynamics, and polarity. Furthermore, this optogenetic toolbox may be exploited in perturbing complex signaling interactions in varied physiological contexts including mammalian embryogenesis.

Construction of a Flexible Optogenetic Device for Multisite and Multiregional Optical Stimulation Through Flexible µ-LED Displays on the Cerebral Cortex.

Precisely delivering light to multiple locations in biological tissue is crucial for advancing multiregional optogenetics in neuroscience research. However, conventional implantable devices typically have rigid geometries and limited light sources, allowing only single or dual probe placement with fixed spacing. Here, a fully flexible optogenetic device with multiple thin-film microscale light-emitting diode (µ-LED) displays scattering from a central controller is presented. Each display is heterogeneously integrated with thin-film 5×10µ-LEDs and five optical fibers 125µm in diameter to achieve cellular-scale spatial resolution. Meanwhile, the device boasts a compact, flexible circuit capable of multichannel configuration and wireless transmission, with an overall weight of 1.31g, enabling wireless, real-time neuromodulation of freely moving rats. Characterization results and finite element analysis have demonstrated excellent optical properties and mechanical stability, while cytotoxicity tests further ensure the biocompatibility of the device for implantable applications. Behavior studies under optogenetic modulation indicate great promise for wirelessly modulating neural functions in freely moving animals. The device with multisite and multiregional optogenetic modulation capability offers a comprehensive platform to advance both fundamental neuroscience studies and potential applications in brain-computer interfaces.

Open-MAC: A low-cost open-source motorized commutator for electro- and opto-physiological recordings in freely moving rodents

In vivo electro- and optophysiology experiments in rodents reveal the neural mechanisms underlying behavior and brain disorders but mostly involve a cable connection between an implant in the animal and an external recording device. Standard tethers with thin cables or non-motorized commutators require constant monitoring and often manual interference to untwist the cable. Motorized commutators offer a solution, but those few that are commercially available are expensive and often not adapted to widely used connector standards of the open-source community like 12-channel SPI. Here we introduce an open-source motorized all-in-one commutator (Open-MAC): a low-cost (240–390 EUR), low-torque motorized commutator that can operate with minimal audible noise in a torque-based mode relying on dual magnetic Hall sensors. It further includes electronics to operate in a torque-free, online pose-estimation-based mode, with future developments. Operation is controlled by an onboard microcontroller (XIAO SAMD21) powered by a USB-C cable or DC power supply. The body and movable parts are 3D-printed. Different Open-MAC versions can support electrophysiology with up to 64 recording channels using the Open-Ephys / IntanTM recording systems as well as miniature endoscope (miniscope) recordings using the UCLA Miniscope v3/4, and can host a fibre for optogenetic modulation.

Fiber-based optrode with microstructured fiber tips for controlled light delivery in optogenetics

Objective. Optogenetic modulation of neuronal activity requires precise and flexible light delivery to deep brain regions. Flat cleaved optical fibers combined with electrodes are widely used in implantable optogenetic devices for light delivery and electrical monitoring of neural activity. However, the flat fiber tip geometry induces serious tissue damage upon insertion, and makes it difficult to adjust and control the spatial extent of illumination within the brain. With their strongly increased tissue-compatibility and the possibility of spatial illumination control, tapered fibers outperform cleaved fibers in targeted neural photo-stimulation. Approach. In this work, we describe our device concept, and present a novel approach for reproducible fabrication of tapered fiber tips via grinding. Furthermore, we characterize recording electrodes by commenting data obtained from electrochemical impedance spectroscopy (EIS). We also investigate the impact of different cone angles (14°, 30°, 60°, and 90°) on the illumination profile and optical throughput. Main results. We fabricated a fiber-based optrode with cone tip and two deposited electrodes. Custom grinding setup for fabrication of tapered fiber tips with various cone angles is developed as a part of our research. Microscope images showed very good optical quality of cone tips. The results of transmitted optical power measurements performed with integrating sphere suggest that, compared to the flat cleaved optical fiber, transmitted power decreases exponentially with cone angle reduction. Obtained emission profiles (as induced fluorescence in Rhodamine 6G water solution) indicate very strong effect of cone angle on shape and size of illumination volume. Results obtained from EIS show the effect of electrode size on its recording capability. Significance. Compared to optrodes with flat cleaved optical fiber, the demonstrated fiber-based optrode with cone tip allows controlled light delivery with reduced invasiveness. The possibility to fabricate reproducible fiber tips with various cone angles enables control of light delivery in optogenetic experiment. The results presented here give neuroscientists the possibility to choose the appropriate tissue-compatible cone geometry depending on their stimulation requirements.

Recent Progress on Transparent Microelectrode-Based Soft Bioelectronic Devices for Neuroscience and Cardiac Research.

Transparent microelectrodes have emerged as promising tools to combine electrical and optical sensing and modulation modalities in many areas of biological and biomedical research. Compared to conventional opaque microelectrodes, they offer a number of specific advantages that can enable advances in functionality and performance. In addition to optical transparency, the mechanical softness feature is desired to minimize foreign body responses, increase biocompatibility, and avoid loss of functionality. In this review, we present recent research from the past several years on transparent microelectrode-based soft bioelectronic devices with an emphasis on their material properties and advanced device designs, as well as multimodal application scenarios for neuroscience and cardiology. First, we introduce material candidates with proper electrical, optical, and mechanical properties for soft transparent microelectrodes. We then discuss examples of soft transparent microelectrode arrays tailored to combine electrical recording and/or stimulation with optical imaging and/or optogenetic modulation of the brain and the heart. Next, we summarize the most recent progress on soft opto-electric devices integrating transparent microelectrodes with microscale light-emitting diodes and/or photodetectors into single and hybrid microsystems as powerful tools to explore the brain and heart functions. A brief overview of possible future directions of soft transparent microelectrode-based biointerfaces is provided to conclude the review.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Photodegradable by Yellow-Orange Light degFusionRed Optogenetic Module with Autocatalytically Formed Chromophore.

Optogenetic systems driven by yellow-orange light are required for the simultaneous regulation of several cellular processes. We have engineered the red fluorescent protein FusionRed into a 26 kDa monomeric optogenetic module, called degFusionRed. Unlike other fluorescent protein-based optogenetic domains, which exhibit light-induced self-inactivation by generating reactive oxygen species, degFusionRed undergoes proteasomal degradation upon illumination with 567 nm light. Similarly to the parent protein, degFusionRed has minimal absorbance at 450 nm and above 650 nm, making it spectrally compatible with blue and near-infrared-light-controlled optogenetic tools. The autocatalytically formed chromophore provides degFusionRed with an additional advantage over most optogenetic tools that require the binding of the exogenous chromophores, the amount of which varies in different cells. The degFusionRed efficiently performed in the engineered light-controlled transcription factor and in the targeted photodegradation of the protein of interest, demonstrating its versatility as the optogenetic module of choice for spectral multiplexed interrogation of various cellular processes.

Characterization and application of several lysis cassettes

Lysis is a common functional module in synthetic biology and is widely used in genetic circuit design. Lysis could be achieved by inducing expression of lysis cassettes originated from phages. However, detailed characterization of lysis cassettes hasn't been reported yet. Here, we first adopted arabinose- and rhamnose-inducible systems to develop inducible expression of five lysis cassettes (S105, A52G, C51S S76C, LKD, LUZ) in Escherichia coli Top10. By measuring OD600, we characterized the lysis behavior of strains harboring different lysis cassettes. These strains were harvested at different growth stages, induced with different concentrations of chemical inducers, or contained plasmids with different copy numbers. We found that although all five lysis cassettes could induce bacterial lysis in Top10, lysis behaviors differed a lot at various conditions. We further found that due to the difference in background expression levels between strain Top10 and Pseudomonas aeruginosa PAO1, it was hard to construct inducible lysis systems in strain PAO1. The lysis cassette controlled by rhamnose-inducible system was finally inserted into the chromosome of strain PAO1 to construct lysis strains after careful screen. The results indicated that LUZ and LKD were more effective in strain PAO1 than S105, A52G and C51S S76C. At last, we constructed an engineered bacteria Q16 using an optogenetic module BphS and the lysis cassette LUZ. The engineered strain was capable of adhering to target surface and achieving light-induced lysis by tuning the strength of ribosome binding sites (RBSs), showing great potential in surface modification.

Wireless Self‐Powered Optogenetic System for Long‐Term Cardiac Neuromodulation to Improve Post‐MI Cardiac Remodeling and Malignant Arrhythmia (Adv. Sci. 9/2023)

Wireless Self-Powered Optogenetic System In article number 2205551, Xiaoya Zhou, Hong Jiang, Lilei Yu, and co-workers introduce a wireless self-powered optogenetic modulation system with which long-term precise cardiac neuromodulation are achieved and the post-MI heart is protected. These findings can be symbolized as the mythical story of Pilgrimage to the West, in which the Incantation for the Golden Hoop kept the Monkey King under control and obtained the precious scriptures.

Selective activation of cholinergic neurotransmission from the medial septal nucleus to hippocampal pyramidal neurones improves sepsis-induced cognitive deficits in mice

BackgroundSepsis-associated encephalopathy is characterised by cognitive dysfunction, and might be mediated by deficits in neurotransmission. Reduced cholinergic neurotransmission in the hippocampus impairs memory function. We assessed real-time alterations of acetylcholine neurotransmission from the medial septal nucleus to the hippocampus, and explored whether sepsis-induced cognitive deficits can be relieved by activating upstream cholinergic projections. MethodLipopolysaccharide (LPS) injection or caecal ligation and puncture (CLP) was used to induce sepsis and associated neuroinflammation in wild-type and mutant mice. Adeno-associated viruses for calcium and acetylcholine imaging, and for optogenetic and chemogenetic modulation of cholinergic neurones were injected into the hippocampus or medial septum, and a 200-μm-diameter optical fibre was implanted to collect acetylcholine and calcium signals. Cholinergic activity of the medial septum was manipulated and combined with cognitive assessment after LPS injection or CLP. ResultsIntracerebroventricular LPS injection reduced postsynaptic acetylcholine (from 0.146 [0.001] to 0.0047 [0.0005]; p=0.004) and calcium (from 0.0236 [0.0075] to 0.0054 [0.0026]; p=0.0388) signals in hippocampal Vglut2-positive glutamatergic neurones, whereas optogenetic activation of cholinergic neurones in the medial septum reversed LPS-induced reductions in these two signals. Intraperitoneal LPS injection decreased acetylcholine concentration in the hippocampus (476 [20] pg ml−1 to 382 [14] pg ml−1; p=0.0001). Reduction in long-term potentiation (238 [23] % to 150 [12] %; p=0.0082) and enhancement of hippocampal pyramidal neurone action potential frequency (5.8 [1.5] Hz to 8.2 [1.8] Hz; p=0.0343) were relieved, and neurocognitive performance was improved by chemogenetic activation of cholinergic innervation of the hippocampus 3 days after LPS injection in septic mice. ConclusionsSystemic or local LPS reduced cholinergic neurotransmission from the medial septum to hippocampal pyramidal neurones, and their selective activation alleviated defects in hippocampal neuronal function and synaptic plasticity and ameliorated memory deficits in sepsis model mice through enhanced cholinergic neurotransmission. This provides a basis for targeting cholinergic signalling to the hippocampus in sepsis-induced encephalopathy.

Wireless Self-Powered Optogenetic System for Long-Term Cardiac Neuromodulation to Improve Post-MI Cardiac Remodeling and Malignant Arrhythmia.

Autonomic imbalance is an important characteristic of patients after myocardial infarction (MI) and adversely contributes to post-MI cardiac remodeling and ventricular arrhythmias (VAs). A previous study proved that optogenetic modulation could precisely inhibit cardiac sympathetic hyperactivity and prevent acute ischemia-induced VAs. Here, a wireless self-powered optogenetic modulation system is introduced, which achieves long-term precise cardiac neuromodulation in ambulatory canines. The wireless self-powered optical system based on a triboelectric nanogenerator is powered by energy harvested from body motion and realized the effective optical illumination that is required for optogenetic neuromodulation (ON). It is further demonstrated that long-term ON significantly mitigates MI-induced sympathetic remodeling and hyperactivity, and improves a variety of clinically relevant outcomes such as improves ventricular dysfunction, reduces infarct size, increases electrophysiological stability, and reduces susceptibility to VAs. These novel insights suggest that wireless ON holds translational potential for the clinical treatment of arrhythmia and other cardiovascular diseases related to sympathetic hyperactivity. Moreover, this innovative self-powered optical system may provide an opportunity to develop implantable/wearable and self-controllable devices for long-term optogenetic therapy.

Highly efficient thin-film 930 nm VCSEL on PDMS for biomedical applications

Recently, biocompatible optical sources have been surfacing for new-rising biomedical applications, allowing them to be used for multi-purpose technologies such as biological sensing, optogenetic modulation, and phototherapy. Especially, vertical-cavity surface-emitting laser (VCSEL) is in the spotlight as a prospective candidate for optical sources owing to its low-driving current performance, low-cost, and package easiness in accordance with two-dimensional (2D) arrays structure. In this study, we successfully demonstrated the actualization of biocompatible thin-film 930 nm VCSELs transferred onto a Polydimethylsiloxane (PDMS) carrier. The PDMS feature with biocompatibility as well as biostability makes the thin-film VCSELs well-suited for biomedical applications. In order to integrate the conventional VCSEL onto the PDMS carrier, we utilized a double-transfer technique that transferred the thin-film VCSELs onto foreign substrates twice, enabling it to maintain the p-on-n polarity of the conventional VCSEL. Additionally, we employed a surface modification-assisted bonding (SMB) using an oxygen plasma in conjunction with silane treatment when bonding the PDMS carrier with the substrate-removed conventional VCSELs. The threshold current and maximum output power of the fabricated 930 nm thin-film VCSELs are 1.08 mA and 7.52 mW at an injection current of 13.9 mA, respectively.

Closed-loop phase-dependent optogenetic modulation of motor cortical theta oscillations

Closed-loop phase-dependent optogenetic modulation of motor cortical theta oscillations

Electrodeposited NaYF4:Yb3+, Er3+ up-conversion films for flexible neural device construction and near-infrared optogenetics.

Near-infrared optogenetics based on up-conversion materials provides a promising tool for the dissection of neural circuit functions in deep brain regions. However, it remains a challenge to combine near-infrared up-conversion optogenetic stimulation with high-density electrophysiological recording in a minimally invasive manner. Here, we develop a flexible device for simultaneous electrophysiological recording and near-infrared optogenetics. The flexible device is constructed by integrating polymer-based flexible recording microelectrodes with electrodeposited NaYF4:Yb3+, Er3+ up-conversion films that can convert deep-tissue-penetrating near-infrared light into visible light for optogenetic activation of C1V1-expressing neurons. The emission properties of the up-conversion films are optimized for green light emission to stimulate C1V1 opsins. Owing to their minimized surgical footprint and high mechanical compliance, chronically implanted devices enable simultaneous electrophysiological recording and near-infrared optogenetic modulation of neuronal activities in the brain.

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation.

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

An adaptive tracking illumination system for optogenetic control of single bacterial cells.

Single-cell behaviors are essential during early-stage biofilm formation. In this study, we aimed to evaluate whether single-cell behaviors could be precisely and continuously manipulated by optogenetics. We thus established adaptive tracking illumination (ATI), a novel illumination method to precisely manipulate the gene expression and bacterial behavior of Pseudomonas aeruginosa on the surface at the single-cell level by using the combination of a high-throughput bacterial tracking algorithm, optogenetic manipulation, and adaptive microscopy. ATI enables precise gene expression control by manipulating the optogenetic module gene expression and type IV pili (TFP)-mediated motility and microcolony formation during biofilm formation through bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) level modifications in single cells. Moreover, we showed that the spatial organization of single cells in mature biofilms could be controlled using ATI. Therefore, this novel method we established might markedly answer various questions or resolve problems in microbiology. KEY POINTS: • High-resolution spatial and continuous optogenetic control of individual bacteria. • Phenotype-specific optogenetic control of individual bacteria. • Capacity to control biologically relevant processes in engineered single cells.

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording.

During the last decade, optogenetics has become an essential tool for the investigation of neural signaling due to its unique capability of selective neural modulation or monitoring. As specific types of neuronal cells can be genetically modified to express opsin proteins, optogenetics enables optical stimulation or inhibition of the selected neurons. There have been several technological advances in the optical system for optogenetics. Recently, it was proposed to combine the optical waveguide for light delivery with electrophysiological recording to simultaneously monitor the neural responses to optogenetic stimulation or inhibition. In this study, an implantable optrode array (2x2 optical fibers) was developed with embedded multichannel electrodes. A light-emitting diode (LED) was employed as a light source, and a microfabricated microlens array was integrated to provide sufficient light power at the tip of the optical fibers. The optrode array system comprises the disposable part and the reusable part. The disposable part has optical fibers and electrodes, while the reusable part has the LED and electronic circuitry for light control and neural signal processing. The novel design of the implantable optrode array system is introduced in the accompanying video in addition to the procedure of the optrode implantation surgery, optogenetic light stimulation, and the electrophysiological neural recording. The results of in vivo experiments successfully showed time-locked neural spikes evoked by the light stimuli from hippocampal excitatory neurons of mice.