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Stimulation triggers endogenous activity patterns in cultured cortical networks.

ABSTRACT: Cultures of dissociated cortical neurons represent a powerful trade-off between more realistic experimental models and abstract modeling approaches, allowing to investigate mechanisms of synchronized activity generation. These networks spontaneously alternate periods of high activity (i.e. network bursts) with periods of quiescence in a dynamic state which recalls the fluctuation of in vivo UP and DOWN states. Network bursts can also be elicited by external stimulation and their spatial propagation patterns tracked by means of multi-channel micro-electrode arrays. In this study, we used rat cortical cultures coupled to micro-electrode arrays to investigate the similarity between spontaneous and evoked activity patterns. We performed experiments by applying electrical stimulation to different network locations and demonstrated that the rank orders of electrodes during evoked and spontaneous events are remarkably similar independently from the stimulation source. We linked this result to the capability of stimulation to evoke firing in highly active and "leader" sites of the network, reliably and rapidly recruited within both spontaneous and evoked bursts. Our study provides the first evidence that spontaneous and evoked activity similarity is reliably observed also in dissociated cortical networks.

SUBMITTER: Pasquale V

PROVIDER: S-EPMC5567348 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Stimulation triggers endogenous activity patterns in cultured cortical networks.

Pasquale Valentina V Martinoia Sergio S Chiappalone Michela M

Scientific reports 20170822 1

Cultures of dissociated cortical neurons represent a powerful trade-off between more realistic experimental models and abstract modeling approaches, allowing to investigate mechanisms of synchronized activity generation. These networks spontaneously alternate periods of high activity (i.e. network bursts) with periods of quiescence in a dynamic state which recalls the fluctuation of in vivo UP and DOWN states. Network bursts can also be elicited by external stimulation and their spatial propagat ...[more]

PMID: 28831071

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Project description:Artificial forms of mechanical limb stimulation are used within multiple fields of study to determine the level of cortical excitability and to map the trajectory of neuronal recovery from cortical damage or disease. Square-wave mechanical or electrical stimuli are often used in these studies, but a characterization of sensory-evoked response properties to square-waves with distinct fundamental frequencies but overlapping harmonics has not been performed. To distinguish between somatic stimuli, the primary somatosensory cortex must be able to represent distinct stimuli with unique patterns of activity, even if they have overlapping features. Thus, mechanical square-wave stimulation was used in conjunction with regional and cellular imaging to examine regional and cellular response properties evoked by different frequencies of stimulation. Flavoprotein autofluorescence imaging was used to map the somatosensory cortex of anaesthetized C57BL/6 mice, and in vivo two-photon Ca2+ imaging was used to define patterns of neuronal activation during mechanical square-wave stimulation of the contralateral forelimb or hindlimb at various frequencies (3, 10, 100, 200, and 300 Hz). The data revealed that neurons within the limb associated somatosensory cortex responding to various frequencies of square-wave stimuli exhibit stimulus-specific patterns of activity. Subsets of neurons were found to have sensory-evoked activity that is either primarily responsive to single stimulus frequencies or broadly responsive to multiple frequencies of limb stimulation. High frequency stimuli were shown to elicit more population activity, with a greater percentage of the population responding and greater percentage of cells with high amplitude responses. Stimulus-evoked cell-cell correlations within these neuronal networks varied as a function of frequency of stimulation, such that each stimulus elicited a distinct pattern that was more consistent across multiple trials of the same stimulus compared to trials at different frequencies of stimulation. The variation in cortical response to different square-wave stimuli can thus be represented by the population pattern of supra-threshold Ca2+ transients, the magnitude and temporal properties of the evoked activity, and the structure of the stimulus-evoked correlation between neurons.

Project description:Abstract Epilepsy in infancy links to a significant risk of neurodevelopmental delay, calling for a better understanding of its underlying mechanisms. Here, we studied cortical activity networks in infants with early-onset epilepsy to identify network properties that could pre-empt infants’ neurodevelopmental course. We studied high-density (64 channel) electroencephalogram during non-rapid eye movement (N2) sleep in n = 49 infants at 1 year of age after being diagnosed with epilepsy during their first year of life. We computed frequency-specific networks in the cortical source space for two intrinsic brain modes: amplitude–amplitude and phase–phase correlations. Cortical activity networks of all frequency bands and connectivity modes were compared between the syndrome groups as well as between the three categories of neurocognitive development. The group differences were studied at three spatial levels: global, regional, and individual connections. Cortical mechanisms related to infant epilepsy were further compared with physiological networks using an automatic spindle detection algorithm. Our results show that global connectivity does not significantly differ between epilepsy syndromes; however, it co-varies with neurocognitive development. The largest network differences were observed at the lowest (<1 Hz) and mid-range (10–15 Hz) frequency bands. An algorithmic removal of sleep spindles from the data partially reduced the mid-range frequency network’s strength. The centrocentral and frontocentral networks at the spindle frequencies were found to be strongest in infants with a persistent age-typical neurocognitive performance, while their low-frequency (< 1 Hz) networks were weaker for both amplitude-amplitude [P = 0.008, effect size = 0.61] and phase–phase correlations (P = 0.02, effect size = 0.54) at low (< 1 Hz). However, subjects with persistent mild neurocognitive delay from 1 to 2 years of age had higher amplitude–amplitude (P = 0.02, effect size = 0.73) and phase–phase (P = 0.06, effect size = 0.59) at low frequencies than those that deteriorated from mild to severely delayed from 1 to 2 years of age. Our findings suggest that cortical activity networks reflect the underlying clinical course of infants’ epilepsy, and measures of spectrally and spatially resolved networks might become useful in better understanding infantile epilepsy as a network disease. Auno et al. report that cortical activity networks examined from the scalp electroencephalogram provide a sensitive measure of brain function. Infants with epilepsy exhibited specific network changes that link to the severity of both current and upcoming neurological outcomes. They may be used for guiding early interventions in infants with epilepsy. Graphical Abstract Graphical abstract

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Stimulation triggers endogenous activity patterns in cultured cortical networks.

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Stimulation triggers endogenous activity patterns in cultured cortical networks.

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