A model of dissociated cortical tissue (original) (raw)
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Biological cybernetics, 2014
This paper describes large-scale simulations of growth, network formation, and behavior in cultures of dissociated cortical cells. A neuron model that incorporates synaptic facilitation/depression and neurite outgrowth/retraction was used to construct virtual cultures of 10,000 cells whose spiking behavior and evolution were investigated in closed-loop simulations. This approach allows us to perform detailed analysis of the effects of model parameters on burst shape and timing, their changes, and the interrelationship among these behaviors, gross network structure, and model parameters. We examined the effects of two parameters--network composition (fraction of excitatory cells) and neuron excitability (activity level corresponding to neurite outgrowth equilibrium)--on network structure and behavior. Our results suggest that much of the burst shape and timing observed in vitro can be explained by a model that includes only closed-loop neurite outgrowth and dynamic synapses; features...
Brain Research, 2006
In vitro cultured neuronal networks coupled to microelectrode arrays (MEAs) constitute a valuable experimental model for studying changes in the neuronal dynamics at different stages of development. After a few days in culture, neurons start to connect each other with functionally active synapses, forming a random network and displaying spontaneous electrophysiological activity. The patterns of collective rhythmic activity change in time spontaneously during in vitro development. Such activity-dependent modifications play a key role in the maturation of the network and reflect changes in the synaptic efficacy, fact widely recognized as a cellular basis of learning, memory and developmental plasticity. Getting advantage from the possibilities offered by the MEAs, the aim of our study is to analyze and characterize the natural changes in dynamics of the electrophysiological activity at different ages of the culture, identifying peculiar steps of the spontaneous evolution of the network. The main finding is that between the second and the third week of culture, the network completely changes its electrophysiological patterns, both in terms of spiking and bursting activity and in terms of cross-correlation between pairs of active channels. Then the maturation process can be characterized by two main phases: modulation and shaping in the synaptic functional connectivity of the network (within the first and second week) and general moderate correlated activity, spread over the entire network, with connections properly formed and stabilized (within the fourth and fifth week).
Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses
Biological Cybernetics, 2010
One of the most specific and exhibited features in the electrical activity of dissociated cultured neural networks (NNs) is the phenomenon of synchronized bursts, whose profiles vary widely in shape, width and firing rate. On the way to understanding the organization and behavior of biological NNs, we reproduced those features with random connectivity network models with 5,000 neurons. While the
Neuroscience Letters, 2004
Spontaneous action potentials were recorded longitudinally for 4 -7 weeks from dissociated rat occipital cortex cells cultured on planar multi-electrode plates, during their development from isolated neurons into synaptically connected neuronal networks. Activity typically consisted of generalized bursts lasting up to several seconds, separated by variable epochs of sporadic firing at some of the active sites. These network bursts displayed discharge patterns with age-dependent firing rate profiles, and durations significantly increasing in the 3rd week in vitro and decreasing after about 1 month in vitro, when they evolved into short events with prompt onsets. These findings indicate that after about a month in vitro these cultured neuronal networks have developed a degree of excitability that allows almost instantaneous triggering of generalized discharges. Individual neurons tend to fire in specific and persistent temporal relationships to one another within these network bursts, suggesting that network connectivity maintains a core topology during its development. q
An extremely rich repertoire of bursting patterns during the development of cortical cultures.
Background: We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities—3000 to 50,000 neurons on areas of 30 to 75 mm2—growing on multi-electrode arrays (MEAs) during the first five weeks of their development. Results: Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure.
Analysis of Cultured Neuronal Networks Using Intraburst Firing Characteristics
IEEE Transactions on Biomedical Engineering, 2008
It is an open question whether neuronal networks, cultured on multielectrode arrays, retain any capability to usefully process information (learning and memory). A necessary prerequisite for learning is that stimulation can induce lasting changes in the network. To observe these changes, one needs a method to describe the network in sufficient detail, while stable in normal circumstances. We analyzed the spontaneous bursting activity that is encountered in dissociated cultures of rat neocortical cells. Burst profiles (BPs) were made by estimating the instantaneous array-wide firing frequency. The shape of the BPs was found to be stable on a time scale of hours. Spatiotemporal detail is provided by analyzing the instantaneous firing frequency per electrode. The resulting phase profiles (PPs) were estimated by aligning BPs to their peak spiking rate over a period of 15 min. The PPs reveal a stable spatiotemporal pattern of activity during bursts over a period of several hours, making them useful for plasticity and learning studies. We also show that PPs can be used to estimate conditional firing probabilities. Doing so, yields an approach in which network bursting behavior and functional connectivity can be studied.
Dynamics and plasticity in developing neuronal networks in vitro
Progress in Brain Research, 2005
When dissociated cortical tissue is brought into culture, neurons readily grow out by forming axonal and dendritic arborizations and synaptic connections. These developing neuronal networks in vitro display spontaneous firing activity from about the end of the first week in vitro. When cultured on multielectrode arrays firing activity can be recorded from many neurons simultaneously over long periods of time.
Collective plasticity and individual stability in cultured neuronal networks
Neurocomputing, 2006
Cultured neuronal networks generate spontaneous activity in the form of synchronized bursting events (SBEs) -short time events during which most of the recorded neurons fire rapidly. Each neuron in the SBE has its own temporal firing rate pattern. It has been shown that a large network can exhibit several SBE sub-groups, each with its own characteristic spatio-temporal pattern of activity. In this work we address the question: what distinguishes one sub-group of SBEs from another? We show that in each SBE type the neurons fire at different delays relative to one another and that in different SBEs the firing rate function of each neuron remains the same.
PLoS ONE, 2013
In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABA A ergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these ''network spikes'' (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts (''bursts of NSs'', BNS), with short (,1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV,0), and weak excitability led to rare BNSs, approaching a Poisson process (CV,. Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV,0.5), with an adaptation timescale in the 2-8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally.