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      Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

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          Abstract

          Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable.

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          Most cited references58

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          Theta oscillations in the hippocampus.

          Theta oscillations represent the "on-line" state of the hippocampus. The extracellular currents underlying theta waves are generated mainly by the entorhinal input, CA3 (Schaffer) collaterals, and voltage-dependent Ca(2+) currents in pyramidal cell dendrites. The rhythm is believed to be critical for temporal coding/decoding of active neuronal ensembles and the modification of synaptic weights. Nevertheless, numerous critical issues regarding both the generation of theta oscillations and their functional significance remain challenges for future research.
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            Large-scale recording of neuronal ensembles.

            How does the brain orchestrate perceptions, thoughts and actions from the spiking activity of its neurons? Early single-neuron recording research treated spike pattern variability as noise that needed to be averaged out to reveal the brain's representation of invariant input. Another view is that variability of spikes is centrally coordinated and that this brain-generated ensemble pattern in cortical structures is itself a potential source of cognition. Large-scale recordings from neuronal ensembles now offer the opportunity to test these competing theoretical frameworks. Currently, wire and micro-machined silicon electrode arrays can record from large numbers of neurons and monitor local neural circuits at work. Achieving the full potential of massively parallel neuronal recordings, however, will require further development of the neuron-electrode interface, automated and efficient spike-sorting algorithms for effective isolation and identification of single neurons, and new mathematical insights for the analysis of network properties.
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              Receptive fields of single neurones in the cat's striate cortex.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                12 October 2011
                14 October 2011
                : 6
                : 10
                : e26204
                Affiliations
                [1 ]Division of Biology, California Institute of Technology, Pasadena, California, United States of America
                [2 ]Kavli Nanoscience Institute, California Institute of Technology, Pasadena, California, United States of America
                [3 ]Broad Fellows Program in Brain Circuitry, California Institute of Technology, Pasadena, California, United States of America
                [4 ]Redwood Center for Theoretical Neuroscience, Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America
                [5 ]Intan Technologies, Los Angeles, California, United States of America
                Max-Planck-Institut für Neurobiologie, Germany
                Author notes

                Conceived and designed the experiments: JD TJB RRH SCM. Performed the experiments: JD TJB RRH SCM. Analyzed the data: JD TJB RRH SCM. Contributed reagents/materials/analysis tools: JD TJB RRH HAL SCM. Wrote the paper: JD TJB RRH HAL SCM.

                Article
                PONE-D-11-15767
                10.1371/journal.pone.0026204
                3192171
                22022568
                6ae3e11c-4717-48a2-8bbc-fb393913bf4a
                Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 13 August 2011
                : 22 September 2011
                Page count
                Pages: 11
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Nervous System Physiology
                Electrophysiology
                Model Organisms
                Animal Models
                Neuroscience
                Behavioral Neuroscience
                Molecular Neuroscience
                Neurophysiology
                Medicine
                Clinical Research Design
                Animal Models of Disease

                Uncategorized
                Uncategorized

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