Burst Detection Methods

Cotterill, Ellese; Eglen, Stephen J.

doi:10.1007/978-3-030-11135-9_8

Cited by 11 publications

(12 citation statements)

References 105 publications

(181 reference statements)

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“…Detection and analysis of synchronous neuronal activity represent a general challenge in neuroscience (Cotterill and Eglen, 2018). To prove that detected population bursts truly reflected synchronous neuronal activity detected by several spatially distributed electrodes, we carefully confirmed the detection of population bursts by comparing MEA recordings with their corresponding spike raster plots and population firing rate diagrams (as described in Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, some of these publications also include calcium imaging data, and the presented calcium traces clearly show asynchronous calcium peaks and the absence of neuronal population wide synchronous activity (Chailangkarn et al, 2016; Monzel et al, 2017). As described recently, the “Poisson surprise method” for the detection of synchronous bursts has limitations such as their tendency to overestimate synchronous bursting in spike trains containing sparse or no synchronous bursting activity (Cotterill and Eglen, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures

et al. 2019

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Reproducibly generating human induced pluripotent stem cell-based functional neuronal circuits, solely obtained from single individuals, poses particular challenges to achieve personalized and patient specific functional neuronal in vitro models. A hallmark of functional neuronal assemblies, synchronous neuronal activity, can be non-invasively studied by microelectrode array (MEA) technology, reliably capturing physiological and pathophysiological aspects of human brain function. In our here presented manuscript, we demonstrate a procedure to generate 3D neural aggregates comprising astrocytes, oligodendroglial cells, and neurons obtained from the same human tissue sample. Moreover, we demonstrate the robust ability of those neurons to create a highly synchronously active neuronal network within 3 weeks in vitro , without additionally applied astrocytes. The fusion of MEA-technology with functional neuronal circuits solely obtained from one individual’s cells represent isogenic person-specific human neuronal sensor chips that pave the way for specific personalized in vitro neuronal networks as well as neurological and neuropsychiatric disease modeling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures

et al. 2019

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“…Considering that P is the probability of N or more APs occurring randomly in a time period of T . NeuroExplorer uses a surprise maximization algorithm ( Legendy and Salcman, 1985 ; Cotterill and Eglen, 2019 ) to find bursts across the AP trains of a single neuron based on following protocol: A burst is identified if three consecutive APs have an ISI of less than half of the average ISI of the spike train. Subsequent APs are added to the initial burst until the ISI becomes larger than the average ISI.…”

Section: Methodsmentioning

confidence: 99%

Long-term morphological and functional dynamics of human stem cell-derived neuronal networks on high-density micro-electrode arrays

et al. 2022

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Comprehensive electrophysiological characterizations of human induced pluripotent stem cell (hiPSC)-derived neuronal networks are essential to determine to what extent these in vitro models recapitulate the functional features of in vivo neuronal circuits. High-density micro-electrode arrays (HD-MEAs) offer non-invasive recording with the best spatial and temporal resolution possible to date. For 3 months, we tracked the morphology and activity features of developing networks derived from a transgenic hiPSC line in which neurogenesis is inducible by neurogenic transcription factor overexpression. Our morphological data revealed large-scale structural changes from homogeneously distributed neurons in the first month to the formation of neuronal clusters over time. This led to a constant shift in position of neuronal cells and clusters on HD-MEAs and corresponding changes in spatial distribution of the network activity maps. Network activity appeared as scarce action potentials (APs), evolved as local bursts with longer duration and changed to network-wide synchronized bursts with higher frequencies but shorter duration over time, resembling the emerging burst features found in the developing human brain. Instantaneous firing rate data indicated that the fraction of fast spiking neurons (150–600 Hz) increases sharply after 63 days post induction (dpi). Inhibition of glutamatergic synapses erased burst features from network activity profiles and confirmed the presence of mature excitatory neurotransmission. The application of GABAergic receptor antagonists profoundly changed the bursting profile of the network at 120 dpi. This indicated a GABAergic switch from excitatory to inhibitory neurotransmission during circuit development and maturation. Our results suggested that an emerging GABAergic system at older culture ages is involved in regulating spontaneous network bursts. In conclusion, our data showed that long-term and continuous microscopy and electrophysiology readouts are crucial for a meaningful characterization of morphological and functional maturation in stem cell-derived human networks. Most importantly, assessing the level and duration of functional maturation is key to subject these human neuronal circuits on HD-MEAs for basic and biomedical applications.

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“…Burst analysis and cross-correlation histograms (CCH) were performed using NeuroExplorer software (Nex technology, Colorado Springs, CO, USA). Burst activity was detected using the Poisson-surprise method (Cotterill and Eglen, 2019).…”

Section: Data Acquisition and Analysismentioning

confidence: 99%

Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons

Tomagra

Franchino²,

Cesano³

et al. 2023

Front. Cell. Neurosci.

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The aim of this work was to monitor the effects of extracellular α-synuclein on the firing activity of midbrain neurons dissociated from substantia nigra TH-GFP mice embryos and cultured on microelectrode arrays (MEA). We monitored the spontaneous firing discharge of the network for 21 days after plating and the role of glutamatergic and GABAergic inputs in regulating burst generation and network synchronism. Addition of GABAA, AMPA and NMDA antagonists did not suppress the spontaneous activity but allowed to identify three types of neurons that exhibited different modalities of firing and response to applied L-DOPA: high-rate (HR) neurons, low-rate pacemaking (LR-p), and low-rate non-pacemaking (LR-np) neurons. Most HR neurons were insensitive to L-DOPA, while the majority of LR-p neurons responded with a decrease of the firing discharge; less defined was the response of LR-np neurons. The effect of exogenous α-synuclein (α-syn) on the firing discharge of midbrain neurons was then studied by varying the exposure time (0–48 h) and the α-syn concentration (0.3–70 μM), while the formation of α-syn oligomers was monitored by means of AFM. Independently of the applied concentration, acute exposure to α-syn monomers did not exert any effect on the spontaneous firing rate of HR, LR-p, and LR-np neurons. On the contrary, after 48 h exposure, the firing activity was drastically altered at late developmental stages (14 days in vitro, DIV, neurons): α-syn oligomers progressively reduced the spontaneous firing discharge (IC50 = 1.03 μM), impaired burst generation and network synchronism, proportionally to the increased oligomer/monomer ratio. Different effects were found on early-stage developed neurons (9 DIV), whose firing discharge remained unaltered, regardless of the applied α-syn concentration and the exposure time. Our findings unravel, for the first time, the variable effects of exogenous α-syn at different stages of midbrain network development and provide new evidence for the early detection of neuronal function impairment associated to aggregated forms of α-syn.

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Burst Detection Methods

Cited by 11 publications

References 105 publications

Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures

Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures

Long-term morphological and functional dynamics of human stem cell-derived neuronal networks on high-density micro-electrode arrays

Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons

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