Large-scale Multimodal Recordings on a High-density Neurochip: Olfactory Bulb and Hippocampal Networks

Emery, Brett; Hu, Xin; Maugeri, Lorenzo; Khanzada, Shahrukh; Klütsch, Diana; Altuntac, Erdem; Amin, Hayder

doi:10.1109/embc48229.2022.9871961

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…Therefore, cell proliferation is determined by the MEA’s area covered with adherent cells, assuming a loss in cell adhesion due to the cytotoxic anti-cancer drug 5-FU ( Akalovich et al, 2021 ; Fohlen et al, 2021 ). Our MEA comprises both subcellular resolution ( Hierlemann et al, 2011 ; Viswam et al, 2018 ; Ell, Zeitler, et al, 2023 ) and cellular network studies ( Amin et al, 2017 ; Viswam et al, 2017 ; Angotzi et al, 2018 ; Abbott et al, 2022 ; Cojocaru et al, 2022 ; Emery et al, 2022 ; 2023 ). To relate electrical imaging to optical imaging, CAN-based images were overlaid with brightfield microscopy images.…”

Section: Introductionmentioning

confidence: 99%

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

Ell,

Bui,

Kigili

et al. 2024

Front. Bioeng. Biotechnol.

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With cancer as one of the leading causes of death worldwide, there is a need for the development of accurate, cost-effective, easy-to-use, and fast drug-testing assays. While the NCI 60 cell-line screening as the gold standard is based on a colorimetric assay, monitoring cells electrically constitutes a label-free and non-invasive tool to assess the cytotoxic effects of a chemotherapeutic treatment on cancer cells. For decades, impedance-based cellular assays extensively investigated various cell characteristics affected by drug treatment but lack spatiotemporal resolution. With progress in microelectrode fabrication, high-density Complementary Metal Oxide Semiconductor (CMOS)-based microelectrode arrays (MEAs) with subcellular resolution and time-continuous recording capability emerged as a potent alternative. In this article, we present a new cell adhesion noise (CAN)-based electrical imaging technique to expand CMOS MEA cell-biology applications: CAN spectroscopy enables drug screening quantification with single-cell spatial resolution. The chemotherapeutic agent 5-Fluorouracil exerts a cytotoxic effect on colorectal cancer (CRC) cells hampering cell proliferation and lowering cell viability. For proof-of-concept, we found sufficient accuracy and reproducibility for CAN spectroscopy compared to a commercially available standard colorimetric biological assay. This label-free, non-invasive, and fast electrical imaging technique complements standardized cancer screening methods with significant advances over established impedance-based approaches.

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Section: Introductionmentioning

confidence: 99%

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

Ell,

Bui,

Kigili

et al. 2024

Front. Bioeng. Biotechnol.

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“…This includes the lack of spatial resolution to accurately map synaptic activity-dependent changes and significant inter-experimental variability that hinder the reproducibility of findings and mask subtle alterations in synaptic plasticity and LTP under different experimental conditions. These limitations have underscored the need for novel large-scale recording techniques that will not only enhance our understanding of the cellular and network mechanisms underlying LTP but also provide a comprehensive spatiotemporal dynamic view of cell assemblies computations in different hippocampal subfields underlying learning and memory processes [18][19][20] . Advanced electrophysiological recording techniques using high-density CMOS-MEAs have revolutionized our understanding of multimodal neural dynamics.…”

Section: Introductionmentioning

confidence: 99%

“…Advanced electrophysiological recording techniques using high-density CMOS-MEAs have revolutionized our understanding of multimodal neural dynamics. These platforms allow simultaneous recording from multiple sites at high spatiotemporal resolution, providing a holistic view of neural interactions [20][21][22][23][24] . In this study, we present EVOX, a high-density, high-resolution electrophysiological platform that enables multisite, long-term, and label-free simultaneous measurements of network-LTP and extracellular evoked synaptic potentials in the hippocampal circuit.…”

Section: Introductionmentioning

confidence: 99%

Mapping Large-scale Spatiotemporal Dynamics of Synaptic Plasticity and LTP for Memory Encoding in the Hippocampal Network

Khanzada,

Hu,

Emery

et al. 2024

Preprint

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Understanding memory formation requires elucidating the intricate dynamics of neuronal networks in the hippocampus, where information is encoded and processed through specific activity patterns and synaptic plasticity. Here, we introduce "EVOX," an advanced network electrophysiology platform equipped with high-density microelectrode arrays to capture critical network-level synaptic dynamics integral to learning and memory. This platform surpasses traditional methods by enabling label-free, high-order mapping of neural interactions, providing unprecedented insights into network Long-Term Potentiation (LTP) and evoked synaptic transmission within the hippocampal network. Utilizing EVOX, we demonstrate that high-frequency stimulation induces network-wide LTP, revealing enhanced synaptic efficacy in previously inactive cell assemblies in hippocampal layers. Our platform enables the real-time observation of network synaptic transmission, capturing the intricate patterns of connectivity and plasticity that underpin memory encoding. Advanced computational techniques further elucidate the mesoscale transmembrane generators and the dynamic processes that govern network-level memory encoding mechanisms. These findings uncover the complex dynamics that underlie learning and memory, showcasing EVOX's potential to explore synaptic and cellular phenomena in aging circuits. EVOX not only advances our understanding of hippocampal memory mechanisms but also serves as a powerful tool to investigate the broader scope of neural plasticity and network interactions in healthy and diseased states.

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“…This clearly falls short of appreciating the diversity of electrical and molecular signals and their interplay underlying brain function, cognition, and behavior 11,12 . But novel brain-on-chip technologies empowered by highdensity complementary metal-oxide semiconductors (CMOS) biosensing microelectrode arrays (CMOS-MEA) are now allowing the non-invasive, multi-site, long-term, and label-free simultaneous measurements of extracellular activity capturing both local field potentials and spiking activity from thousands of neurons with single-cell accuracy without disruption of cellular integrity [13][14][15][16][17] . Merging these cutting-edge technologies would potentiate the insight to be gained from decoding the spatiotemporal electrophysiological and transcriptomics information in the same tissue while retaining cell positioning.…”

Section: Introductionmentioning

confidence: 99%

MEA-seqX: High-resolution Profiling of Large-scale Electrophysiological and Transcriptional Network Dynamics

Emery,

Hu,

Klütsch

et al. 2024

Preprint

Self Cite

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Concepts of brain function imply congruence and mutual causal influence between molecular events and neuronal activity. Decoding entangled information from concurrent molecular and electrophysiological network events demands innovative methodology bridging scales and modalities. Our MEA-seqX platform, integrating high-density microelectrode arrays, spatial transcriptomics, optical imaging, and advanced computational strategies, enables the simultaneous recording and analysis of molecular and electrical network activities at the level of individual cells. Applied to a mouse hippocampal model of experience-dependent plasticity, MEA-seqX unveiled massively enhanced nested dynamics between transcription and function. Graph-theoretic analysis revealed an increase in densely connected bimodal hubs, marking the first observation of coordinated spatiotemporal dynamics in hippocampal circuitry at both molecular and functional levels. This platform also identified different cell types based on their distinct bimodal profiles. Machine-learning algorithms accurately predicted network-wide electrophysiological features from spatial gene expression, demonstrating a previously inaccessible convergence across modalities, time, and scales.

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Large-scale Multimodal Recordings on a High-density Neurochip: Olfactory Bulb and Hippocampal Networks

Cited by 7 publications

References 14 publications

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

Mapping Large-scale Spatiotemporal Dynamics of Synaptic Plasticity and LTP for Memory Encoding in the Hippocampal Network

MEA-seqX: High-resolution Profiling of Large-scale Electrophysiological and Transcriptional Network Dynamics

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