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A key aspect of how the brain learns and enables decision-making processes is through synaptic interactions. Electrical transmission and communication in a network of synapses are modulated by extracellular fields generated by ionic chemical gradients. Emulating such spatial interactions in synthetic networks can be of potential use for neuromorphic learning and the hardware implementation of artificial intelligence. Here, we demonstrate that in a network of hydrogen-doped perovskite nickelate devices, electric bias across a single junction can tune the coupling strength between the neighboring cells. Electrical transport measurements and spatially resolved diffraction and nanoprobe X-ray and scanning microwave impedance spectroscopic studies suggest that graded proton distribution in the inhomogeneous medium of hydrogen-doped nickelate film enables this behavior. We further demonstrate signal integration through the coupling of various junctions.
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Real-time spike sorting and processing are crucial for closed-loop brain-machine interfaces and neural prosthetics. Recent developments in high-density multi-electrode arrays with hundreds of electrodes have enabled simultaneous recordings of spikes from a large number of neurons. However, the high channel count imposes stringent demands on real-time spike sorting hardware regarding data transmission bandwidth and computation complexity. Thus, it is necessary to develop a specialized real-time hardware that can sort neural spikes on the fly with high throughputs while consuming minimal power. Here, we present a real-time, low latency spike sorting processor that utilizes high-density CuOx resistive crossbars to implement in-memory spike sorting in a massively parallel manner. We developed a fabrication process which is compatible with CMOS BEOL integration. We extensively characterized switching characteristics and statistical variations of the CuOx memory devices. In order to implement spike sorting with crossbar arrays, we developed a template matching-based spike sorting algorithm that can be directly mapped onto RRAM crossbars. By using synthetic and in vivo recordings of extracellular spikes, we experimentally demonstrated energy efficient spike sorting with high accuracy. Our neuromorphic interface offers substantial improvements in area (~1000× less area), power (~200× less power), and latency (4.8µs latency for sorting 100 channels) for real-time spike sorting compared to other hardware implementations based on FPGAs and microcontrollers.
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New devices that use targeted electrical stimulation to treat refractory localization-related epilepsy have shown great promise, although it is not well known which targets most effectively prevent the initiation and spread of seizures. To better understand how the brain transitions from healthy to seizing on a local scale, we induced focal epileptiform activity in the visual cortex of five anesthetized cats with local application of the GABAA blocker picrotoxin while simultaneously recording local field potentials on a high-resolution electrocorticography array and laminar depth probes. Epileptiform activity appeared in the form of isolated events, revealing a consistent temporal pattern of ictogenesis across animals with interictal events consistently preceding the appearance of seizures. Based on the number of spikes per event, there was a natural separation between seizures and shorter interictal events. Two distinct spatial regions were seen: an epileptic focus that grew in size as activity progressed, and an inhibitory surround that exhibited a distinct relationship with the focus both on the surface and in the depth of the cortex. Epileptiform activity in the cortical laminae was seen concomitant with activity on the surface. Focus spikes appeared earlier on electrodes deeper in the cortex, suggesting that deep cortical layers may be integral to recruiting healthy tissue into the epileptic network and could be a promising target for interventional devices. Our study may inform more effective therapies to prevent seizure generation and spread in localization-related epilepsies. NEW & NOTEWORTHY We induced local epileptiform activity and recorded continuous, high-resolution local field potentials from the surface and depth of the visual cortex in anesthetized cats. Our results reveal a consistent pattern of ictogenesis, characterize the spatial spread of the epileptic focus and its relationship with the inhibitory surround, and show that focus activity within events appears earliest in deeper cortical layers. These findings have potential implications for the monitoring and treatment of refractory epilepsy.
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Excitabilidade Cortical , Epilepsia Resistente a Medicamentos/fisiopatologia , Neocórtex/fisiologia , Animais , Gatos , Masculino , Neocórtex/fisiopatologiaRESUMO
The last decades have witnessed substantial progress in optical technologies revolutionizing our ability to record and manipulate neural activity in genetically modified animal models. Meanwhile, human studies mostly rely on electrophysiological recordings of cortical potentials, which cannot be inferred from optical recordings, leading to a gap between our understanding of dynamics of microscale populations and brain-scale neural activity. By enabling concurrent integration of electrical and optical modalities, transparent graphene microelectrodes can close this gap. However, the high impedance of graphene constitutes a big challenge towards the widespread use of this technology. Here, we experimentally demonstrate that this high impedance of graphene microelectrodes is fundamentally limited by quantum capacitance. We overcome this quantum capacitance limit by creating a parallel conduction path using platinum nanoparticles. We achieve a 100 times reduction in graphene electrode impedance, while maintaining the high optical transparency crucial for deep 2-photon microscopy. Using a transgenic mouse model, we demonstrate simultaneous electrical recording of cortical activity with high fidelity while imaging calcium signals at various cortical depths right beneath the transparent microelectrodes. Multimodal analysis of Ca2+ spikes and cortical surface potentials offers unique opportunities to bridge our understanding of cellular dynamics and brain-scale neural activity.
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Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.
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Implantes Absorvíveis , Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiologia , Eletrodos Implantados , Silício , Animais , Mapeamento Encefálico/instrumentação , Mapeamento Encefálico/métodos , Ratos , Silício/química , Silício/farmacologiaRESUMO
Optically transparent neural microelectrodes have facilitated simultaneous electrophysiological recordings from the brain surface with the optical imaging and stimulation of neural activity. A remaining challenge is to scale down the electrode dimensions to the single-cell size and increase the density to record neural activity with high spatial resolution across large areas to capture nonlinear neural dynamics. Here we developed transparent graphene microelectrodes with ultrasmall openings and a large, transparent recording area without any gold extensions in the field of view with high-density microelectrode arrays up to 256 channels. We used platinum nanoparticles to overcome the quantum capacitance limit of graphene and to scale down the microelectrode diameter to 20 µm. An interlayer-doped double-layer graphene was introduced to prevent open-circuit failures. We conducted multimodal experiments, combining the recordings of cortical potentials of microelectrode arrays with two-photon calcium imaging of the mouse visual cortex. Our results revealed that visually evoked responses are spatially localized for high-frequency bands, particularly for the multiunit activity band. The multiunit activity power was found to be correlated with cellular calcium activity. Leveraging this, we employed dimensionality reduction techniques and neural networks to demonstrate that single-cell and average calcium activities can be decoded from surface potentials recorded by high-density transparent graphene arrays.
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Grafite , Nanopartículas Metálicas , Camundongos , Animais , Cálcio , Eletrodos Implantados , Platina , MicroeletrodosRESUMO
CMOS-RRAM integration holds great promise for low energy and high throughput neuromorphic computing. However, most RRAM technologies relying on filamentary switching suffer from variations and noise, leading to computational accuracy loss, increased energy consumption, and overhead by expensive program and verify schemes. We developed a filament-free, bulk switching RRAM technology to address these challenges. We systematically engineered a trilayer metal-oxide stack and investigated the switching characteristics of RRAM with varying thicknesses and oxygen vacancy distributions to achieve reliable bulk switching without any filament formation. We demonstrated bulk switching at megaohm regime with high current nonlinearity, up to 100 levels without compliance current. We developed a neuromorphic compute-in-memory platform and showcased edge computing by implementing a spiking neural network for an autonomous navigation/racing task. Our work addresses challenges posed by existing RRAM technologies and paves the way for neuromorphic computing at the edge under strict size, weight, and power constraints.
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In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.
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Eletrônica , Modelos Neurológicos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Sinapses , Animais , Humanos , NeurôniosRESUMO
Brain-inspired computing is an emerging field, which aims to extend the capabilities of information technology beyond digital logic. A compact nanoscale device, emulating biological synapses, is needed as the building block for brain-like computational systems. Here, we report a new nanoscale electronic synapse based on technologically mature phase change materials employed in optical data storage and nonvolatile memory applications. We utilize continuous resistance transitions in phase change materials to mimic the analog nature of biological synapses, enabling the implementation of a synaptic learning rule. We demonstrate different forms of spike-timing-dependent plasticity using the same nanoscale synapse with picojoule level energy consumption.
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Encéfalo/fisiologia , Eletrônica , Nanotecnologia , Microscopia Eletrônica de Transmissão , SinapsesRESUMO
The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on in vivo hippocampal activity dynamics mostly relies on single modalities, such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. Here, we develop the E-Cannula, integrating fully transparent graphene microelectrodes with imaging cannula, which enables simultaneous electrical recording and two-photon calcium imaging from the exact same neural populations across an anatomically extended region of the mouse hippocampal CA1 stably across several days. The large-scale multimodal recordings show that sharp wave ripples (SWRs) exhibit spatiotemporal wave patterns along multiple axes in two-dimensional (2D) space with different spatial extents and temporal propagation modes. Notably, distinct SWR wave patterns are associated with the selective recruitment of orthogonal CA1 cell assemblies. These results demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components.
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Grafite , Memória Episódica , Animais , Região CA1 Hipocampal , Cálcio , Cânula , Hipocampo , CamundongosRESUMO
Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain.
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Neurônios , Córtex Visual , Humanos , Animais , Camundongos , Neurônios/fisiologia , Encéfalo , Próteses e Implantes , Organoides/transplante , Córtex Visual/fisiologiaRESUMO
Objective. Electrical recordings of neural activity from brain surface have been widely employed in basic neuroscience research and clinical practice for investigations of neural circuit functions, brain-computer interfaces, and treatments for neurological disorders. Traditionally, these surface potentials have been believed to mainly reflect local neural activity. It is not known how informative the locally recorded surface potentials are for the neural activities across multiple cortical regions.Approach. To investigate that, we perform simultaneous local electrical recording and wide-field calcium imaging in awake head-fixed mice. Using a recurrent neural network model, we try to decode the calcium fluorescence activity of multiple cortical regions from local electrical recordings.Main results. The mean activity of different cortical regions could be decoded from locally recorded surface potentials. Also, each frequency band of surface potentials differentially encodes activities from multiple cortical regions so that including all the frequency bands in the decoding model gives the highest decoding performance. Despite the close spacing between recording channels, surface potentials from different channels provide complementary information about the large-scale cortical activity and the decoding performance continues to improve as more channels are included. Finally, we demonstrate the successful decoding of whole dorsal cortex activity at pixel-level using locally recorded surface potentials.Significance. These results show that the locally recorded surface potentials indeed contain rich information of the large-scale neural activities, which could be further demixed to recover the neural activity across individual cortical regions. In the future, our cross-modality inference approach could be adapted to virtually reconstruct cortex-wide brain activity, greatly expanding the spatial reach of surface electrical recordings without increasing invasiveness. Furthermore, it could be used to facilitate imaging neural activity across the whole cortex in freely moving animals, without requirement of head-fixed microscopy configurations.
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Interfaces Cérebro-Computador , Animais , Encéfalo , Potenciais Evocados , Camundongos , Redes Neurais de Computação , VigíliaRESUMO
Many cognitive processes require communication between the neocortex and the hippocampus. However, coordination between large-scale cortical dynamics and hippocampal activity is not well understood, partially due to the difficulty in simultaneously recording from those regions. In the present study, we developed a flexible, insertable and transparent microelectrode array (Neuro-FITM) that enables investigation of cortical-hippocampal coordinations during hippocampal sharp-wave ripples (SWRs). Flexibility and transparency of Neuro-FITM allow simultaneous recordings of local field potentials and neural spiking from the hippocampus during wide-field calcium imaging. These experiments revealed that diverse cortical activity patterns accompanied SWRs and, in most cases, cortical activation preceded hippocampal SWRs. We demonstrated that, during SWRs, different hippocampal neural population activity was associated with distinct cortical activity patterns. These results suggest that hippocampus and large-scale cortical activity interact in a selective and diverse manner during SWRs underlying various cognitive functions. Our technology can be broadly applied to comprehensive investigations of interactions between the cortex and other subcortical structures.
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Potenciais de Ação/fisiologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Imagem Multimodal/métodos , Neocórtex/diagnóstico por imagem , Neocórtex/fisiologia , Animais , Eletrodos Implantados , Feminino , Hipocampo/química , Masculino , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Microeletrodos , Imagem Multimodal/instrumentação , Neocórtex/química , Optogenética/instrumentação , Optogenética/métodosRESUMO
To circumvent the von Neumann bottleneck, substantial progress has been made towards in-memory computing with synaptic devices. However, compact nanodevices implementing non-linear activation functions are required for efficient full-hardware implementation of deep neural networks. Here, we present an energy-efficient and compact Mott activation neuron based on vanadium dioxide and its successful integration with a conductive bridge random access memory (CBRAM) crossbar array in hardware. The Mott activation neuron implements the rectified linear unit function in the analogue domain. The neuron devices consume substantially less energy and occupy two orders of magnitude smaller area than those of analogue complementary metal-oxide semiconductor implementations. The LeNet-5 network with Mott activation neurons achieves 98.38% accuracy on the MNIST dataset, close to the ideal software accuracy. We perform large-scale image edge detection using the Mott activation neurons integrated with a CBRAM crossbar array. Our findings provide a solution towards large-scale, highly parallel and energy-efficient in-memory computing systems for neural networks.
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Computadores , Nanotecnologia/instrumentação , Redes Neurais de Computação , Benchmarking , Bases de Dados Factuais , Desenho de Equipamento , Neurônios/fisiologia , Óxidos/química , Compostos de Vanádio/químicaRESUMO
OBJECTIVE: To investigate chronic durability of transparent graphene electrodes fabricated on polyethylene terephthalate (PET) and SU-8 substrates for chronic in vivo studies. METHODS: We perform systematic accelerated aging tests to understand the chronic reliability and failure modes of transparent graphene microelectrode arrays built on PET and SU-8 substrates. We employ graphene microelectrodes fabricated on PET substrate in chronic in vivo experiments with transgenic mice. RESULTS: Our results show that graphene microelectrodes fabricated on PET substrate work reliably after 30 days accelerated aging test performed at 87 °C, equivalent to 960 days in vivo lifetime. We demonstrate stable chronic recordings of cortical potentials in multimodal imaging/recording experiments using transparent graphene microelectrodes fabricated on PET substrate. On the other hand, graphene microelectrode arrays built on SU-8 substrate exhibit extensive crack formation across microelectrode sites and wires after one to two weeks, resulting in total failure of recording capability for chronic studies. CONCLUSION: PET shows superior reliability as a substrate for graphene microelectrode arrays for chronic in vivo experiments. SIGNIFICANCE: Graphene is a unique neural interface material enabling cross-talk free integration of electrical and optical recording and stimulation techniques in the same experiment. To date, graphene-based microelectrode arrays have been demonstrated in various multi-modal acute experiments involving electrophysiological sensing or stimulation, optical imaging and optogenetics stimulation. Understanding chronic reliability of graphene-based transparent interfaces is very important to expand the use of this technology for long-term behavioral studies with animal models.
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Grafite , Animais , Eletrodos Implantados , Camundongos , Microeletrodos , Optogenética , Reprodutibilidade dos TestesRESUMO
The hippocampus plays important roles in memory formation and retrieval through sharp-wave-ripples. Recent studies have shown that certain neuron populations in the prefrontal cortex (PFC) exhibit coordinated reactivations during awake ripple events. These experimental findings suggest that the awake ripple is an important biomarker, through which the hippocampus interacts with the neocortex to assist memory formation and retrieval. However, the computational mechanisms of this ripple based hippocampal-cortical coordination are still not clear due to the lack of unified models that include both the hippocampal and cortical networks. In this work, using a coupled biophysical model of both CA1 and PFC, we investigate possible mechanisms of hippocampal-cortical memory trace transfer and the conditions that assist reactivation of the transferred memory traces in the PFC. To validate our model, we first show that the local field potentials generated in the hippocampus and PFC exhibit ripple range activities that are consistent with the recent experimental studies. Then we demonstrate that during ripples, sequence replays can successfully transfer the information stored in the hippocampus to the PFC recurrent networks. We investigate possible mechanisms of memory retrieval in PFC networks. Our results suggest that the stored memory traces in the PFC network can be retrieved through two different mechanisms, namely the cell-specific input representing external stimuli and non-specific spontaneous background noise representing spontaneous memory recall events. Importantly, in both cases, the memory reactivation quality is robust to network connection loss. Finally, we find out that the quality of sequence reactivations is enhanced by both increased number of SWRs and an optimal background noise intensity, which tunes the excitability of neurons to a proper level. Our study presents a mechanistic explanation for the memory trace transfer from the hippocampus to neocortex through ripple coupling in awake states and reports two different mechanisms by which the stored memory traces can be successfully retrieved.
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Inspired from the computational efficiency of the biological brain, spiking neural networks (SNNs) emulate biological neural networks, neural codes, dynamics, and circuitry. SNNs show great potential for the implementation of unsupervised learning using in-memory computing. Here, we report an algorithmic optimization that improves energy efficiency of online learning with SNNs on emerging non-volatile memory (eNVM) devices. We develop a pruning method for SNNs by exploiting the output firing characteristics of neurons. Our pruning method can be applied during network training, which is different from previous approaches in the literature that employ pruning on already-trained networks. This approach prevents unnecessary updates of network parameters during training. This algorithmic optimization can complement the energy efficiency of eNVM technology, which offers a unique in-memory computing platform for the parallelization of neural network operations. Our SNN maintains ~90% classification accuracy on the MNIST dataset with up to ~75% pruning, significantly reducing the number of weight updates. The SNN and pruning scheme developed in this work can pave the way toward applications of eNVM based neuro-inspired systems for energy efficient online learning in low power applications.
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Propagating waves along the cortical surface have recently attracted significant attention by the neuroscience community. However, whether these propagating waves imply network connectivity changes for the neural circuits is not known. In this work, we employ a high density porous graphene microelectrode array and perform in vivo experiments with rodents to investigate network connectivity during cortical propagating waves. The spatial-temporal analysis of the cortical recordings reveals various types of propagating waves across the recording area. Network analysis results show that these propagating waves are consistent with the functional connectivity changes in the neural circuits, suggesting that the underlying network states are reflected by the cortical potential propagation patterns.
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Grafite , Microeletrodos , Córtex Motor/fisiologia , Rede Nervosa , Córtex Somatossensorial/fisiologia , Animais , Camundongos , Análise Espaço-TemporalRESUMO
Cortical propagating waves have recently attracted significant attention by the neuroscience community. These travelling waves have been suggested to coordinate different brain areas and play roles in assisting neural plasticity and learning. However, it is extremely challenging to record them with very fine spatial scales over large areas to investigate their effect on neural dynamics or network connectivity changes. In this work, we employ high-density porous graphene microelectrode arrays fabricated using laser pyrolysis on flexible substrates to study the functional network connectivity during cortical propagating waves. The low-impedance porous graphene arrays are used to record cortical potentials during theta oscillations and drug-induced seizures in vivo. Spatiotemporal analysis on the neural recordings reveal that theta oscillations and epileptiform activities have distinct characteristics in terms of both synchronization and resulting propagating wave patterns. To investigate the network connectivity during the propagating waves, we perform network analysis. The results show that the propagating waves are consistent with the functional connectivity changes in the neural circuits, suggesting that the underlying network states are reflected by the cortical potential propagation patterns.
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Córtex Cerebral/fisiologia , Grafite/química , Microeletrodos , Modelos Neurológicos , Rede Nervosa/fisiologia , Crânio/fisiologia , Animais , Plasticidade Neuronal , Porosidade , Ratos , Análise Espaço-TemporalRESUMO
Electrophysiology is a decades-old technique widely used for monitoring activity of individual neurons and local field potentials. Optogenetics has revolutionized neuroscience studies by offering selective and fast control of targeted neurons and neuron populations. The combination of these two techniques is crucial for causal investigation of neural circuits and understanding their functional connectivity. However, electrical artifacts generated by light stimulation interfere with neural recordings and hinder the development of compact closed-loop systems for precise control of neural activity. Here, we demonstrate that transparent graphene micro-electrodes fabricated on a clear polyethylene terephthalate film eliminate the light-induced artifact problem and allow development of a compact battery-powered closed-loop optogenetics system. We extensively investigate light-induced artifacts for graphene electrodes in comparison to metal control electrodes. We then design optical stimulation module using micro-LED chips coupled to optical fibers to deliver light to intended depth for optogenetic stimulation. For artifact-free integration of graphene micro-electrode recordings with optogenetic stimulation, we design and develop a compact closed-loop system and validate it for different frequencies of interest for neural recordings. This compact closed-loop optogenetics system can be used for various applications involving optogenetic stimulation and electrophysiological recordings.