Ex vivo cultured neuronal networks emit in vivo-like spontaneous activity

Okamoto, Kazuki; Ishikawa, Tomoe; Abe, Reimi; Ishikawa, Daisuke; Mizunuma, Mika; Norimoto, Hiroaki; Matsuki, Norio; Ikegaya, Yuji

doi:10.1007/s12576-014-0337-4

Cited by 20 publications

(17 citation statements)

References 47 publications

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“…However, our primary interest was to see whether in principle the feature space can be reliably separated with standard approaches [ 18 ]. Similar machine-learning methods are not yet routinely used in analysing spontaneous activity, although see [ 20 ] for a recent example showing how single-cell activity could be classified as either in vivo or in vitro . Finally, with the advent of a new generation of higher density MEAs containing up to 4,096 electrodes [ 21 ], it is likely that there are much richer patterns of activity than we describe here.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that other in vitro methods, such as brain slices, might produce more realistic activity patterns of spontaneous activity [ 26 ]. Recent machine-learning approaches have suggested, however, that cultured neurons generate spontaneous activity patterns more similar to in vivo activity than activity from organotypic slices [ 20 ]. However, we make no strong claims about whether our recordings from networks of cultured neurons can tell us about in vivo activity patterns; we believe that both cultured networks and slice preparations are only simple approximations to in vivo networks.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

et al. 2015

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BackgroundNeural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks.ResultsWe used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every 2 or 3 days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 days in vitro. We quantified the activity patterns in hippocampal and cortical networks using 11 features. Three out of 11 features showed striking differences in activity between hippocampal and cortical networks: (1) interburst intervals are less variable in spike trains from hippocampal cultures; (2) hippocampal networks have higher correlations and (3) hippocampal networks generate more robust theta-bursting patterns. Machine-learning techniques confirmed that these differences in patterning are sufficient to classify recordings reliably at any given age as either hippocampal or cortical networks.ConclusionsAlthough cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising the phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

et al. 2015

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“…However, our primary interest was to see whether in principle the feature space can be reliably separated with standard approaches [15]. Similar machine learning methods are not yet routinely used in analysing spontaneous activity, although see [17] for a recent example showing how singlecell activity could be classified as either in vivo or in vitro . Finally, with the advent of a new generation of higher density MEAs containing up 4096 electrodes [18], it is likely that there are much richer patterns of activity than we describe here.…”

Section: Discussionmentioning

confidence: 99%

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

Charlesworth

Cotterill

Morton

et al. 2014

Preprint

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Background: Neural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks. Results: We used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every 2 or 3 days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 days in vitro. We quantified the activity patterns in hippocampal and cortical networks using 11 features. Three out of 11 features showed striking differences in activity between hippocampal and cortical networks: (1) interburst intervals are less variable in spike trains from hippocampal cultures; (2) hippocampal networks have higher correlations and (3) hippocampal networks generate more robust theta-bursting patterns. Machine-learning techniques confirmed that these differences in patterning are sufficient to classify recordings reliably at any given age as either hippocampal or cortical networks. Conclusions: Although cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising the phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.

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“…We used hippocampal slice cultures because they have low light scattering and provide a unique opportunity for high-speed, large-scale optical recordings of spontaneous calcium activity from hundreds of spines (11). In these ex vivo preparations, hippocampal networks self-reorganize to emit spontaneous neuronal activity that resembles in vivo neuronal activity (19), which includes SWs with repeated spike sequences (20,21). We found that neurons that fired spikes frequently in SWs received transient synaptic inputs during SWs.…”

Section: Introductionmentioning

confidence: 99%

Locally sequential synaptic reactivation during hippocampal ripples

Ishikawa

Ikegaya

2020

Sci. Adv.

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The sequential reactivation of memory-relevant neuronal ensembles during hippocampal sharp-wave (SW) ripple oscillations reflects cognitive processing. However, how a downstream neuron decodes this spatiotemporally organized activity remains unexplored. Using subcellular calcium imaging from CA1 pyramidal neurons in ex vivo hippocampal networks, we discovered that neighboring spines are activated serially along dendrites toward or away from cell bodies. Sequential spine activity was engaged repeatedly in different SWs in a complex manner. In a single SW event, multiple sequences appeared discretely in dendritic trees, but overall, sequences occurred preferentially in some dendritic branches. Thus, sequential replays of multineuronal spikes are distributed across several compartmentalized dendritic foci of a postsynaptic neuron, with their spatiotemporal features preserved.

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Ex vivo cultured neuronal networks emit in vivo-like spontaneous activity

Cited by 20 publications

References 47 publications

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

Locally sequential synaptic reactivation during hippocampal ripples

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