Spike sorting of synchronous spikes from local neuron ensembles

Synchronous spike discharge of cortical neurons is thought to be a fingerprint of neuronal cooperativity. Because neighboring neurons are more densely connected to one another than neurons that are located further apart, near-synchronous spike discharge can be expected to be prevalent and it might provide an important basis for cortical computations. Using microelectrodes to record local groups of neurons does not allow for the reliable separation of synchronous spikes from different cells, because available spike sorting algorithms cannot correctly resolve the temporally overlapping waveforms. We show that high spike sorting performance of in vivo recordings, including overlapping spikes, can be achieved with a recently developed filter-based template matching procedure. Using tetrodes with a three-dimensional structure, we demonstrate with simulated data and ground truth in vitro data, obtained by dual intracellular recording of two neurons located next to a tetrode, that the spike sorting of synchronous spikes can be as successful as the spike sorting of nonoverlapping spikes and that the spatial information provided by multielectrodes greatly reduces the error rates. We apply the method to tetrode recordings from the prefrontal cortex of behaving primates, and we show that overlapping spikes can be identified and assigned to individual neurons to study synchronous activity in local groups of neurons.

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Fast and accurate spike sorting in vitro and in vivo for up to thousands of electrodes

10.1101/067843 ◽

2016 ◽

Cited By ~ 22

Author(s):

Pierre Yger ◽

Giulia L.B. Spampinato ◽

Elric Esposito ◽

Baptiste Lefebvre ◽

Stéphane Deny ◽

...

Keyword(s):

Template Matching ◽

Large Scale ◽

Ground Truth ◽

Spike Sorting ◽

Electrode Arrays ◽

Ground Truth Data ◽

Sorting Problem ◽

Large Populations

AbstractUnderstanding how assemblies of neurons encode information requires recording large populations of cells in the brain. In recent years, multi-electrode arrays and large silicon probes have been developed to record simultaneously from hundreds or thousands of electrodes packed with a high density. However, these new devices challenge the classical way to do spike sorting. Here we developed a new method to solve these issues, based on a highly automated algorithm to extract spikes from extracellular data, and show that this algorithm reached near optimal performance both in vitro and in vivo. The algorithm is composed of two main steps: 1) a “template-finding” phase to extract the cell templates, i.e. the pattern of activity evoked over many electrodes when one neuron fires an action potential; 2) a “template-matching” phase where the templates were matched to the raw data to find the location of the spikes. The manual intervention by the user was reduced to the minimal, and the time spent on manual curation did not scale with the number of electrodes. We tested our algorithm with large-scale data from in vitro and in vivo recordings, from 32 to 4225 electrodes. We performed simultaneous extracellular and patch recordings to obtain “ground truth” data, i.e. cases where the solution to the sorting problem is at least partially known. The performance of our algorithm was always close to the best expected performance. We thus provide a general solution to sort spikes from large-scale extracellular recordings.

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How do spike collisions affect spike sorting performance?

10.1101/2021.11.29.470450 ◽

2021 ◽

Author(s):

Samuel Garcia ◽

Alessio Buccino ◽

Pierre Yger

Keyword(s):

Template Matching ◽

Ground Truth ◽

Spatial Density ◽

Neuron Activity ◽

Spike Sorting ◽

Extracellular Signals ◽

New Generation ◽

Single Neuron Activity

Recently, a new generation of devices have been developed to record neural activity simultaneously from hundreds of electrodes with a very high spatial density, both for in vitro and in vivo applications. While these advances enable to record from many more cells, they also dramatically increase the amount overlapping "synchronous" spikes (colliding in space and/or in time), challenging the already complicated process of spike sorting (i.e. extracting isolated single-neuron activity from extracellular signals). In this work, we used synthetic ground-truth recordings to quantitatively benchmark the performance of state-of-the-art spike sorters focusing specifically on spike collisions. Our results show that while modern template-matching based algorithms are more accurate than density-based approaches, all methods, to some extent, failed to detect synchronous spike events of neurons with similar extracellular signals. Interestingly, the performance of the sorters is not largely affected by the the spiking activity in the recordings, with respect to average firing rates and spike-train correlation levels.

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TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

Cell Death and Disease ◽

10.1038/s41419-020-03278-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yan Zhou ◽

Tao Tao ◽

Guangjie Liu ◽

Xuan Gao ◽

Yongyue Gao ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Therapeutic Target ◽

Cortical Neurons ◽

Neuronal Apoptosis ◽

Early Brain Injury ◽

Neurological Deficits ◽

Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

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Machine learning-based classification of mitochondrial morphology in primary neurons and brain

Scientific Reports ◽

10.1038/s41598-021-84528-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Garrett M. Fogo ◽

Anthony R. Anzell ◽

Kathleen J. Maheras ◽

Sarita Raghunayakula ◽

Joseph M. Wider ◽

...

Keyword(s):

Image Analysis ◽

Cortical Neurons ◽

Mitochondrial Dynamics ◽

Automated Image Analysis ◽

Mitochondrial Morphology ◽

Analysis Pipeline ◽

Genetic Ablation ◽

Block Face

AbstractThe mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.

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Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from ischemic/anoxic injury in vitro and in vivo

Neuroscience ◽

10.1016/j.neuroscience.2006.10.043 ◽

2007 ◽

Vol 144 (4) ◽

pp. 1509-1515 ◽

Cited By ~ 31

Author(s):

H.-S. Sun ◽

Z.-P. Feng ◽

P.A. Barber ◽

A.M. Buchan ◽

R.J. French

Keyword(s):

Potassium Channels ◽

Cortical Neurons ◽

Anoxic Injury

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Protein Folding: Search for Basic Physical Models

The Scientific World JOURNAL ◽

10.1100/tsw.2003.50 ◽

2003 ◽

Vol 3 ◽

pp. 623-635 ◽

Cited By ~ 3

Author(s):

Ivan Y. Torshin ◽

Robert W. Harrison

Keyword(s):

Protein Folding ◽

Tertiary Structure ◽

Three Dimensional ◽

Physical Models ◽

Dimensional Structure ◽

Computational Techniques ◽

Linear Sequence ◽

Physical Forces

How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context ofin vivoprotein folding (which has been studied only for a few proteins), the roles of the fundamental physical forces in thein vitrofolding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces). Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.

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KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation

Human Molecular Genetics ◽

10.1093/hmg/ddq280 ◽

2010 ◽

Vol 19 (18) ◽

pp. 3642-3651 ◽

Cited By ~ 30

Author(s):

Maria M. Alves ◽

Grzegorz Burzynski ◽

Jean-Marie Delalande ◽

Jan Osinga ◽

Annemieke van der Goot ◽

...

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Neuronal Differentiation ◽

Cortical Neurons ◽

Neuronal Development ◽

Direct Interaction ◽

Clinical Disorder ◽

Neurite Development

Abstract Goldberg–Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo . To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

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A MICROCALORIMETRIC STUDY OF TURTLE CORTICAL SLICES: INSIGHTS INTO BRAIN METABOLIC DEPRESSION

Journal of Experimental Biology ◽

10.1242/jeb.191.1.141 ◽

1994 ◽

Vol 191 (1) ◽

pp. 141-153 ◽

Cited By ~ 1

Author(s):

C Doll ◽

P Hochachka ◽

S Hand

Keyword(s):

Cortical Neurons ◽

Heat Dissipation ◽

Energy Charge ◽

Utilization Rate ◽

Rapid Decline ◽

Metabolic Depression ◽

Slice Preparation ◽

Cortical Slices

In previous papers, we have examined turtle cortical neurons in vitro for mechanisms of anoxic metabolic depression ('channel arrest' and changes in electrical parameters). Negative results prompted the current study with the aim of examining more closely the energy profile and metabolism of turtle cortical slices. Calorimetry is used to measure heat dissipation during normoxia and nitrogen perfusion (120 min) and the results are converted into an ATP utilization rate. These indicate that the control rate of ATP utilization (1.72 µmol ATP g-1 min-1) agrees closely with in vivo whole-brain metabolic measurements. Both nitrogen perfusion and pharmacologically induced anoxic (cyanide+N2) groups depressed heat dissipation considerably compared with the control value (nitrogen 37 %; pharmacological anoxia 49 %). The resulting ATP utilization estimates indicate metabolic depressions of 30 % (nitrogen) and 42 % (pharmacological anoxia). The slice preparation did not exhibit a change in any measured adenylate parameter for up to 120 min of anoxia or pharmacological anoxia. Significant changes did occur in [ADP], ATP/ADP ratio and energy charge after 240 min of exposure to anoxic conditions. These results support the idea that the turtle cortical slice preparation has a profound resistance to anoxia, with both nitrogen perfusion and pharmacological anoxia causing a rapid decline in heat dissipation and metabolism.

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Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs

eLife ◽

10.7554/elife.41563 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 3

Author(s):

Nathan T Henderson ◽

Sylvain J Le Marchand ◽

Martin Hruska ◽

Simon Hippenmeyer ◽

Liqun Luo ◽

...

Keyword(s):

Cortical Neurons ◽

Spine Density ◽

Cell Competition ◽

Intrinsic Factors ◽

Genetic Mouse Model ◽

Synapse Density ◽

A Cell ◽

Cell Cell

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.

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Modulator of apoptosis-1 is a potential therapeutic target in acute ischemic injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x18794839 ◽

2018 ◽

Vol 39 (12) ◽

pp. 2406-2418 ◽

Cited By ~ 3

Author(s):

Su Jing Chan ◽

Hui Zhao ◽

Kazuhide Hayakawa ◽

Chou Chai ◽

Chong Teik Tan ◽

...

Keyword(s):

Cortical Neurons ◽

Infarct Volume ◽

Neuronal Loss ◽

Ischemic Injury ◽

Glucose Deprivation ◽

Artery Occlusion ◽

In Vivo Models ◽

The Brain

Modulator of apoptosis 1 (MOAP-1) is a Bax-associating protein highly enriched in the brain. In this study, we examined the role of MOAP-1 in promoting ischemic injuries following a stroke by investigating the consequences of MOAP-1 overexpression or deficiency in in vitro and in vivo models of ischemic stroke. MOAP-1 overexpressing SH-SY5Y cells showed significantly lower cell viability following oxygen and glucose deprivation (OGD) treatment when compared to control cells. Consistently, MOAP-1−/− primary cortical neurons were observed to be more resistant against OGD treatment than the MOAP-1+/+ primary neurons. In the mouse transient middle cerebral artery occlusion (tMCAO) model, ischemia triggered MOAP-1/Bax association, suggested activation of the MOAP-1-dependent apoptotic cascade. MOAP-1−/− mice were found to exhibit reduced neuronal loss and smaller infarct volume 24 h after tMCAO when compared to MOAP-1+/+ mice. Correspondingly, MOAP-1−/− mice also showed better integrity of neurological functions as demonstrated by their performance in the rotarod test. Therefore, both in vitro and in vivo data presented strongly support the conclusion that MOAP-1 is an important apoptotic modulator in ischemic injury. These results may suggest that a reduction of MOAP-1 function in the brain could be a potential therapeutic approach in the treatment of acute stroke.

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