Local Field Potentials
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Novel Methods for Assessing Electrophysiological Function of Cardiac and Neural 3D Cell Cultures with MEA Technology
. Novel methods for assessing electrophysiological function of cardiac and neural 3D cell cultures with MEA technology Anthony Nicolini, Denise Sullivan, Heather Hayes, Andrew Wilsie, Rob Grier, Daniel Millard Axion BioSystems, Atlanta, GA Multiwell MEA Technology MEA Assay with Cardiomyocytes MEA Assay with Neurons Microelectrode array technology Functional Cardiac Phenotypes Functional Neuronal Phenotypes The flexibility and accessibility of neuronal and The need for simple, reliable, and predictive pre-clinical assays for drug discovery (e.g. “disease-in-a-dish” AxIS Navigator analysis software provides straightforward reporting of multiple measures of cell culture maturity. cardiac in vitro models, particularly induced models) and safety have motivated the development of 2D and 3D in vitro models with human stem cell- pluripotent stem cell (iPSC) technology, has allowed (a) (c) Action derived cardiomyocytes. The Maestro MEA platform enables assessment of functional in vitro cardiomyocyte complex human biology to be reproduced in vitro at Potential activity with an easy-to-use benchtop system. The Maestro detects and records signals from cells cultured unimaginable scales. Accurate characterization of directly onto an array of planar electrodes in each well of the MEA plate, with each of the following four modes Field neurons and cardiomyocytes requires an assay that providing critical information for in vitro assessment: Potential provides a functional phenotype. Measurements of electrophysiological activity across a networked • Field Potential – “gold standard” measurement for multiwell cardiac electrophysiology. population offer a comprehensive characterization Clinical • Action Potential – first scalable technique for acquiring action potential signals from intact cardiac models. beyond standard genomic and biochemical ECG • Propagation – detect speed and direction of action potential propagation. -
SELF-PROPAGATING, NON-SYNAPTIC HIPPOCAMPAL WAVES RECRUIT NEURONS by ELECTRIC FIELD COUPLING by RAJAT SHAMACHAR SHIVACHARAN Submi
SELF-PROPAGATING, NON-SYNAPTIC HIPPOCAMPAL WAVES RECRUIT NEURONS BY ELECTRIC FIELD COUPLING By RAJAT SHAMACHAR SHIVACHARAN Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Advisor: Dominique M. Durand, PhD Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May 2019 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis dissertation of Rajat Shamachar Shivacharan candidate for the degree of Doctor of Philosophy*. Committee Chair Jeffrey R. Capadona Thesis Advisor/Committee Member Dominque M. Durand Committee Member Cameron C. McIntyre Committee Member Hillel J. Chiel Date of Defense: April 8th, 2019 *We also certify that written approval has been obtained for any proprietary material contained therein. Dedication To my great grandfathers, Mr. Doddappa Acharya and Mr. Shilipi Shamachar; to my grandparents Mr. Y.S. Shamachar & Mrs. Lalitha, and Mr. H.D. Ramakrishna Sastry & Justice B.S. Indrakala; for being exemplary role models for me, and for being the luminaries of my family. To my Mom & Dad, my brother Manju, our loving, four-legged pup Rocky, and the rest of my family and friends near and far; for your unwavering love and support throughout my adventures. Table of Contents Contents Table of Contents ............................................................................................................... i List of Figures ................................................................................................................. -
Climbing Fiber Synapses Rapidly Inhibit Neighboring Purkinje Cells Via Ephaptic Coupling
bioRxiv preprint doi: https://doi.org/10.1101/2019.12.17.879890; this version posted December 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Climbing fiber synapses rapidly inhibit neighboring Purkinje cells via ephaptic coupling Kyung-Seok Han*, Christopher H. Chen*, Mehak M. Khan, Chong Guo and Wade G. Regehr1 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA *Co-first author 1Lead Contact Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2019.12.17.879890; this version posted December 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Climbing fibers (CFs) from the inferior olive (IO) provide strong excitatory inputs onto the dendrites of cerebellar Purkinje cells (PC), and trigger distinctive responses known as complex spikes (CSs). We find that in awake, behaving mice, a CS in one PC suppresses conventional simple spikes (SSs) in neighboring PCs for several milliseconds. This involves a novel form of ephaptic coupling, in which an excitatory synapse nonsynaptically inhibits neighboring cells by generating large negative extracellular signals near their dendrites. The distance dependence of CS-SS ephaptic signaling, combined with the known divergence of CF synapses made by IO neurons, allows a single IO neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over one hundred PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicate that such brief PC suppression can effectively promote firing in neurons in the deep cerebellar nuclei and motor thalamus. -
1 Title Neuronal Coupling by Endogenous Electric Fields
Title Neuronal coupling by endogenous electric fields: Cable theory and applications to coincidence detector neurons in the auditory brainstem Authors Joshua H. Goldwyn1,2,3 John Rinzel1,2 Contributions JHG and JR designed study, analyzed data, and wrote manuscript. JHG performed simulations. Affiliations 1 Center for Neural Science, New York University, New York, NY, United States 2 Courant Institute of Mathematical Sciences, New York University, New York, NY, United States 3 Department of Mathematics, Ohio State University, Columbus, OH, United States Running Head Neuronal coupling by endogenous electric fields Address for Correspondence Joshua H. Goldwyn 100 Math Tower 231 West 18th Avenue Columbus OH, 43210-1174 Phone: 614-292-5256 Fax: 614 292-1479 Email: [email protected] 1 Abstract The ongoing activity of neurons generates a spatially- and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these “ephaptic interactions” are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude and this Ve perturbs the Vm of “nearby” cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brainstem. The MSO is a possible locus of ephaptic interactions: sounds evoke large Ve in vivo in this nucleus (millivolt-scale). -
Intrinsic Dendritic Filtering Gives Low-Pass Power Spectra of Local Field Potentials
J Comput Neurosci DOI 10.1007/s10827-010-0245-4 Intrinsic dendritic filtering gives low-pass power spectra of local field potentials Henrik Lindén · Klas H. Pettersen · Gaute T. Einevoll Received: 31 August 2009 / Revised: 30 March 2010 / Accepted: 6 May 2010 © Springer Science+Business Media, LLC 2010 Abstract The local field potential (LFP) is among the the LFP. The frequency dependence of the properties most important experimental measures when probing of the current dipole moment set up by the synaptic in- neural population activity, but a proper understanding put current is found to qualitatively account for several of the link between the underlying neural activity and salient features of the observed LFP. Two approximate the LFP signal is still missing. Here we investigate this schemes for calculating the LFP, the dipole approxima- link by mathematical modeling of contributions to the tion and the two-monopole approximation, are tested LFP from a single layer-5 pyramidal neuron and a and found to be potentially useful for translating results single layer-4 stellate neuron receiving synaptic input. from large-scale neural network models into predic- An intrinsic dendritic low-pass filtering effect of the tions for results from electroencephalographic (EEG) LFP signal, previously demonstrated for extracellular or electrocorticographic (ECoG) recordings. signatures of action potentials, is seen to strongly affect the LFP power spectra, even for frequencies as low as Keywords Local field potential · Single neuron · 10 Hz for the example pyramidal neuron. Further, the Forward modeling · Frequency dependence · EEG LFP signal is found to depend sensitively on both the recording position and the position of the synaptic in- put: the LFP power spectra recorded close to the active synapse are typically found to be less low-pass filtered 1 Introduction than spectra recorded further away. -
Hebbian and Neuromodulatory Mechanisms Interact to Trigger
Hebbian and neuromodulatory mechanisms interact to PNAS PLUS trigger associative memory formation Joshua P. Johansena,b,c,1,2, Lorenzo Diaz-Mataixc,1, Hiroki Hamanakaa, Takaaki Ozawaa, Edgar Ycua, Jenny Koivumaaa, Ashwani Kumara, Mian Houc, Karl Deisserothd,e, Edward S. Boydenf, and Joseph E. LeDouxc,g,2 aLaboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; bDepartment of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-0198, Japan; cCenter for Neural Science, New York University, New York, NY 10003; dDepartment of Bioengineering, Department of Psychiatry and Behavioral Sciences, and eHoward Hughes Medical Institute, Stanford University, Stanford, CA 94305; fMcGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and gThe Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962 Contributed by Joseph E. LeDoux, November 7, 2014 (sent for review March 11, 2014) A long-standing hypothesis termed “Hebbian plasticity” suggests auditory threat (fear) conditioning (23, 24) is a form of asso- that memories are formed through strengthening of synaptic con- ciative learning during which a neutral auditory conditioned nections between neurons with correlated activity. In contrast, stimulus (CS) is temporally paired with an aversive unconditioned other theories propose that coactivation of Hebbian and neuro- stimulus (US), often a mild electric shock (17, 20, 21, 25–27). modulatory processes produce the synaptic strengthening that Following training, the auditory CS comes to elicit behavioral underlies memory formation. Using optogenetics we directly tested defense responses (such as freezing) and supporting physiologi- whether Hebbian plasticity alone is both necessary and sufficient to cal changes controlled by the autonomic nervous and endocrine produce physiological changes mediating actual memory formation systems. -
Independent Components Analysis of Local Field Potential Sources in the Primate Superior Colliculus
Independent Components Analysis of Local Field Potential Sources in the Primate Superior Colliculus by Yu Liu B.S. in Telecommunication Engineering, Nanjing University of Posts and Telecommunications, 2017 Submitted to the Graduate Faculty of the Swanson School of Engineering in partial fulfillment of the requirements for the degree of Master of Science University of Pittsburgh 2019 UNIVERSITY OF PITTSBURGH SWANSON SCHOOL OF ENGINEERING This thesis was presented by Yu Liu It was defended on July 17, 2019 and approved by Ahmed Dallal, Ph.D., Assistant Professor, Department of Electrical and Computer Engineering Neeraj Gandhi, Ph.D., Professor, Department of Bioengineering Amro El-Jaroudi, Ph.D., Associate Professor, Department of Electrical and Computer Engineering Zhi-Hong Mao, Ph.D., Professor, Department of Electrical and Computer Engineering Thesis Advisors: Ahmed Dallal, Ph.D., Assistant Professor, Department of Electrical and Computer Engineering, Neeraj Gandhi, Ph.D., Professor, Department of Bioengineering ii Copyright c by Yu Liu 2019 iii Independent Components Analysis of Local Field Potential Sources in the Primate Superior Colliculus Yu Liu, M.S. University of Pittsburgh, 2019 When visually-guided eye movements (saccades) are produced, some signal-available elec- trical potentials are recorded by electrodes in the superior colliculus (SC), which is ideal to investigate communication between the different layers due to the laminar organization and structured anatomical connections within SC. The first step to realize this objective is iden- tifying the location of signal-generators involved in the procedure. Local Field Potential (LFP), representing a combination of the various generators measured in the vicinity of each electrodes, makes this issue as similar as blind source separation problem. -
Arxiv:2007.00031V2 [Q-Bio.NC] 11 Aug 2020
Bringing Anatomical Information into Neuronal Network Models S.J. van Albada1;2, A. Morales-Gregorio1;3, T. Dickscheid4, A. Goulas5, R. Bakker1;6, S. Bludau4, G. Palm1, C.-C. Hilgetag5;7, and M. Diesmann1;8;9 1Institute of Neuroscience and Medicine (INM-6) Computational and Systems Neuroscience, Institute for Advanced Simulation (IAS-6) Theoretical Neuroscience, and JARA-Institut Brain Structure-Function Relationships (INM-10), Jülich Research Centre, Jülich, Germany 2Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, Germany 3RWTH Aachen University, Aachen, Germany 4Institute of Neuroscience and Medicine (INM-1) Structural and Functional Organisation of the Brain, Jülich Research Centre, Jülich, Germany 5Institute of Computational Neuroscience, University Medical Center Eppendorf, Hamburg, Germany 6Department of Neuroinformatics, Donders Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands 7Department of Health Sciences, Boston University, Boston, USA 8Department of Psychiatry, Psychotherapy and Psychosomatics, School of Medicine, RWTH Aachen University, Aachen, Germany 9Department of Physics, Faculty 1, RWTH Aachen University, Aachen, Germany Abstract For constructing neuronal network models computational neu- roscientists have access to wide-ranging anatomical data that neverthe- less tend to cover only a fraction of the parameters to be determined. Finding and interpreting the most relevant data, estimating missing val- ues, and combining the data and estimates from various sources into a coherent whole is a daunting task. With this chapter we aim to provide guidance to modelers by describing the main types of anatomical data that may be useful for informing neuronal network models. We further discuss aspects of the underlying experimental techniques relevant to the interpretation of the data, list particularly comprehensive data sets, and describe methods for filling in the gaps in the experimental data. -
Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis Samuel Stuart Mcafee University of Tennessee Health Science Center
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 12-2017 Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis Samuel Stuart McAfee University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Medical Neurobiology Commons Recommended Citation McAfee, Samuel Stuart (http://orcid.org/0000-0003-4121-0592), "Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis" (2017). Theses and Dissertations (ETD). Paper 448. http://dx.doi.org/10.21007/ etd.cghs.2017.0445. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Biomedical Sciences Track Neuroscience Research Advisor Detlef H. Heck, Ph.D. Committee Max L. Fletcher, Ph.D. Robert C. Foehring, Ph.D. Shalini Narayana, Ph.D. Robert J. Ogg, Ph.D. ORCID http://orcid.org/0000-0003-4121-0592 DOI 10.21007/etd.cghs.2017.0445 This dissertation is available at UTHSC Digital Commons: https://dc.uthsc.edu/dissertations/448 Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis A Dissertation Presented for The Graduate Studies Council The University of Tennessee Health Science Center In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy From The University of Tennessee By Samuel Stuart McAfee December 2017 Portions of Chapter 5 © 2016 by Elsevier BV. -
Axonal Computations
REVIEW published: 18 September 2019 doi: 10.3389/fncel.2019.00413 Axonal Computations Pepe Alcami 1,2* and Ahmed El Hady 3,4* 1 Division of Neurobiology, Department of Biology II, Ludwig-Maximilians-Universitaet Muenchen, Martinsried, Germany, 2 Department of Behavioural Neurobiology, Max Planck Institute for Ornithology, Seewiesen, Germany, 3 Princeton Neuroscience Institute, Princeton University, Princeton, NJ, United States, 4 Howard Hughes Medical Institute, Princeton University, Princeton, NJ, United States Axons functionally link the somato-dendritic compartment to synaptic terminals. Structurally and functionally diverse, they accomplish a central role in determining the delays and reliability with which neuronal ensembles communicate. By combining their active and passive biophysical properties, they ensure a plethora of physiological computations. In this review, we revisit the biophysics of generation and propagation of electrical signals in the axon and their dynamics. We further place the computational abilities of axons in the context of intracellular and intercellular coupling. We discuss how, by means of sophisticated biophysical mechanisms, axons expand the repertoire of axonal computation, and thereby, of neural computation. Keywords: analog-digital signaling, action potential generation, propagation, resistance, capacitance, myelin, Edited by: axo-axonal coupling Dominique Debanne, INSERM U1072 Neurobiologie des canaux Ioniques et de la Synapse, 1. INTRODUCTION France Reviewed by: Neurons are compartmentalized into input compartments formed by dendrites and somas, and Mickael Zbili, an output compartment, the axon. However, in the current era, there is a widespread tendency to INSERM U1028 Centre de Recherche consider that the biophysics of single neurons do not matter to understand neuronal dynamics and en Neurosciences de Lyon, France Alon Korngreen, behavior. -
The Information Content of Local Field Potentials: Experiments and Models
The information content of Local Field Potentials: experiments and models Alberto Mazzoni a, Nikos K. Logothetis b, c, Stefano Panzeri a,d * a Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Via Bettini 31, 38068 Rovereto (TN), Italy b Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany c Division of Imaging Science and Biomedical Engineering, University of Manchester, Manchester M13 9PT, United Kingdom d Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QB, United Kingdom * Corresponding author: S. Panzeri, email: [email protected] Keywords: Vision, recurrent networks, integrate and fire, LFP modelling, neural code, spike timing, natural movies, mutual information, oscillations, gamma band 1 1. Local Field Potential dynamics offer insights into the function of neural circuits The Local Field Potential (LFP) is a massed neural signal obtained by low pass‐filtering (usually with a cutoff low‐pass frequency in the range of 100‐300 Hz) of the extracellular electrical potential recorded with intracranial electrodes. LFPs have been neglected for a few decades because in‐vivo neurophysiological research focused mostly on isolating action potentials from individual neurons, but the last decade has witnessed a renewed interested in the use of LFPs for studying cortical function, with a large amount of recent empirical and theoretical neurophysiological studies using LFPs to investigate the dynamics and the function of neural circuits under different conditions. There are many reasons why the use of LFP signals has become popular over the last 10 years. Perhaps the most important reason is that LFPs and their different band‐limited components (known e.g. -
The Origin of Extracellular Fields and Currents — EEG, Ecog, LFP and Spikes
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Rev Manuscript Author Neurosci. Author Manuscript Author manuscript; available in PMC 2016 June 14. Published in final edited form as: Nat Rev Neurosci. ; 13(6): 407–420. doi:10.1038/nrn3241. The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes György Buzsáki1,2,3, Costas A. Anastassiou4, and Christof Koch4,5 1Center for Molecular and Behavioural Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, New Jersey 07102, USA 2New York University Neuroscience Institute, New York University Langone Medical Center, New York, New York 10016, USA 3Center for Neural Science, New York University, New York, New York 10003, USA 4Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA 5Allen Institute for Brain Science, 551 North 34th Street, Seattle, Washington 98103, USA Abstract Neuronal activity in the brain gives rise to transmembrane currents that can be measured in the extracellular medium. Although the major contributor of the extracellular signal is the synaptic transmembrane current, other sources — including Na+ and Ca2+ spikes, ionic fluxes through voltage- and ligand-gated channels, and intrinsic membrane oscillations — can substantially shape the extracellular field. High-density recordings of field activity in animals and subdural grid recordings in humans, combined with recently developed data processing tools and computational modelling, can provide insight into the cooperative behaviour of neurons, their average synaptic input and their spiking output, and can increase our understanding of how these processes contribute to the extracellular signal. Electric current contributions from all active cellular processes within a volume of brain tissue superimpose at a given location in the extracellular medium and generate a potential, Ve (a scalar measured in Volts), with respect to a reference potential.