recording-analyzing-multimodal-large-scale-neuronal-ensemble-dynamics

Recording and Analyzing Multimodal Large-Scale Neuronal Ensemble Dynamics on CMOS-Integrated High-Density Microelectrode Array

Large-scale neuronal networks and their complex distributed microcircuits are essential to generate perception, cognition, and behavior that emerge from ...

German Center for Neurodegenerative Diseases (DZNE)

Large-scale multi-site biosensors are essential to probe the olfactory bulb (OB) circuitry for understanding the spatiotemporal dynamics of simultaneous discharge patterns. Current ex-vivo biosensing techniques are limited to recording a small set of neurons and cannot provide an adequate resolution, which hinders revealing the fast dynamic underlying the information coding mechanisms in the OB circuit. Here, we demonstrate a novel biohybrid OB-CMOS biosensing platform to decipher the cross-scale dynamics of the OB electrogenesis and quantify the distinct neuronal coding properties. The approach with 4096-microelectrodes offers a non-invasive, label-free, bioelectrical imaging to decode simultaneous firing patterns from thousands of connected neuronal ensembles in acute OB slices. The platform can measure spontaneous and drug-induced extracellular field potential activity with substantially improved spatiotemporal resolution over conventional OB-based biosensors. Also, we employ our OB-CMOS recordings to perform multidimensional analysis to instantiate specific neurophysiological metrics underlying the olfactory spatiotemporal coding that emerged from the OB interconnected layers. Our results delineate the computational implications of large-scale activity patterns in functional olfactory processing. The systematic interplay of the experimental CMOS-base platform architecture and the high-content characterization of the olfactory circuit with various computational analyses endow significant functional interrogations of the OB information processing, high-spatiotemporal connectivity mapping, and global circuit dynamics. Thus, our study can inspire the design of advanced biomimetic olfactory-based biosensors and neuromorphic approaches for diagnostic biomarkers and drug discovery applications.

Implementation of biohybrid olfactory bulb on a high-density CMOS-chip to reveal large-scale spatiotemporal circuit information.

Experiential richness creates tissue-level changes and synaptic plasticity as patterns emerge from rhythmic spatiotemporal activity of large interconnected neuronal assemblies. Despite numerous experimental and computational approaches at different scales, the precise impact of experience on network-wide computational dynamics remains inaccessible due to the lack of applicable large-scale recording methodology. We here demonstrate a large-scale multi-site biohybrid brain circuity on-CMOS-based biosensor with an unprecedented spatiotemporal resolution of 4096 microelectrodes, which allows simultaneous electrophysiological assessment across the entire hippocampal-cortical subnetworks from mice living in an enriched environment (ENR) and standard-housed (SD) conditions. Our platform, empowered with various computational analyses, reveals environmental enrichment's impacts on local and global spatiotemporal neural dynamics, firing synchrony, topological network complexity, and large-scale connectome. Our results delineate the distinct role of prior experience in enhancing multiplexed dimensional coding formed by neuronal ensembles and error tolerance and resilience to random failures compared to standard conditions. The scope and depth of these effects highlight the critical role of high-density, large-scale biosensors to provide a new understanding of the computational dynamics and information processing in multimodal physiological and experience-dependent plasticity conditions and their role in higher brain functions. Knowledge of these large-scale dynamics can inspire the development of biologically plausible computational models and computational artificial intelligence networks and expand the reach of neuromorphic brain-inspired computing into new applications.

Article	Year
Implementation of biohybrid olfactory bulb on a high-density CMOS-chip to reveal large-scale spatiotemporal circuit information. Biosensors & bioelectronics\| PubMed ID: 34852985	2022
High-resolution CMOS-based biosensor for assessing hippocampal circuit dynamics in experience-dependent plasticity. Biosensors & bioelectronics\| PubMed ID: 37379793	2023

Shahrukh Khanzada

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