Spontaneous coordinated activity in cultured networks: Analysis of multiple ignition sites, primary circuits, and burst phase delay distributions

Ham, Michael; Bettencourt, Luís M. A.; McDaniel, F. D.; Gross, Guenter W.

doi:10.1007/s10827-007-0059-1

Cited by 73 publications

(70 citation statements)

References 38 publications

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“…Eytan and Marom (2006) called them 'privileged' neurons; Latham et al (2000b) described them as endogenously active cells, about 32% of all cells. On average 17% of spontaneously active neurons can be referred to as burst leaders, as reported by Ham et al (2008). In our own lab we often find 2 or 3 (out of 60) electrodes with 'pacemakerlike' activity, which is about 4%.…”

Section: Network With 'Pacemaker-driven' Activitymentioning

confidence: 52%

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

et al. 2010

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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 common approach to induce bursting behavior in neuronal network models is noise injection, there is experimental evidence suggesting the existence of pacemaker-like neurons. In our simulations noise did evoke bursts, but with an unrealistically gentle rising slope. We show that a small subset of 'pacemaker' neurons can trigger bursts with a more realistic profile. We found that adding pacemaker-like neurons as well as adaptive synapses yield burst features (shape, width, and height of the main phase) in the same ranges as obtained experimentally. Finally, we demonstrate how changes in network connectivity, transmission delays, and excitatory fraction influence network burst features quantitatively.

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Section: Network With 'Pacemaker-driven' Activitymentioning

confidence: 52%

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

et al. 2010

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“…Stimulation sites were selected from ranks 1-5, i.e., electrodes at which activity, on average, appeared early in a burst. This procedure identified so-called "early-to-fire" neurons or "major burst leader" (Eytan and Marom 2006;Ham et al 2008). Stimuli were delivered to a single site in almost all experiments; only when it is mentioned explicitly were stimuli delivered to two sites simultaneously.…”

Section: Methodsmentioning

confidence: 99%

Quantitative examination of stimulus-response relations in cortical networks in vitro

Weihberger

Okujeni

Mikkonen

et al. 2013

Journal of Neurophysiology

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Variable responses of neuronal networks to repeated sensory or electrical stimuli reflect the interaction of the stimulus' response with ongoing activity in the brain and its modulation by adaptive mechanisms, such as cognitive context, network state, or cellular excitability and synaptic transmission capability. Here, we focus on reliability, length, delays, and variability of evoked responses with respect to their spatial distribution, interaction with spontaneous activity in the networks, and the contribution of GABAergic inhibition. We identified network-intrinsic principles that underlie the formation and modulation of spontaneous activity and stimulus-response relations with the use of state-dependent stimulation in generic neuronal networks in vitro. The duration of spontaneously recurring network-wide bursts of spikes was best predicted by the length of the preceding interval. Length, delay, and structure of responses to identical stimuli systematically depended on stimulus timing and distance to the stimulation site, which were described by a set of simple functions of spontaneous activity. Response length at proximal recording sites increased with the duration of prestimulus inactivity and was best described by a saturation function y(t) ϭ A(1 Ϫ e Ϫ␣t ). Concomitantly, the delays of polysynaptic late responses at distant sites followed an exponential decay y(t) ϭ Be Ϫ␤t ϩ C. In addition, the speed of propagation was determined by the overall state of the network at the moment of stimulation. Disinhibition increased the number of spikes/network burst and interburst interval length at unchanged gross firing rate, whereas the response modulation by the duration of prestimulus inactivity was preserved. Our data suggest a process of network depression during bursts and subsequent recovery that limit evoked responses following distinct rules. We discuss shortterm synaptic depression due to depletion of neurotransmitter vesicles as an underlying mechanism. The seemingly unreliable patterns of spontaneous activity and stimulus-response relations thus follow a predictable structure determined by the interdependencies of network structures and activity states.

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“…Cluster processing was enriched by means of an outlier-removal procedure that discarded the units whose Mahalanobis distances from the centroid of the cluster were greater than the fixed threshold at 1.4. To analyze the burst structure, we applied a running window of variable duration (10 milliseconds to 1 second), 27 in order to detect burst duration (BD). Moreover, we identified the number of spikes engaged in each burst (SN), the spike rate (SR), and the interburst interval (IBI).…”

Section: Mea Electrophysiologymentioning

confidence: 99%

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Orlando¹,

Cazzaniga²,

Tringali³

et al. 2017

IJN

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Purpose Mesoporous silica nanoparticles (MSNPs) are excellent candidates for biomedical applications and drug delivery to different human body areas, the brain included. Although toxicity at cellular level has been investigated, we are still far from using MSNPs in the clinic, because the mechanisms involved in the cellular responses activated by MSNPs have not yet been elucidated. Materials and methods This study used an in vitro multiparametric approach to clarify relationships among size, dose, and time of exposure of MSNPs (0.05–1 mg/mL dose range), and cellular responses by analyzing the morphology, viability, and functionality of human vascular endothelial cells and neurons. Results The results showed that 24 hours of exposure of endothelial cells to 250 nm MSNPs exerted higher toxicity in terms of mitochondrial activity and membrane integrity than 30 nm MSN at the same dose. This was due to induced cell autophagy (in particular mitophagy), probably consequent to MSNP cellular uptake (>20%). Interestingly, after 24 hours of treatment with 30 nm MSNPs, very low MSNP uptake (<1%) and an increase in nitric oxide production (30%, P <0.01) were measured. This suggests that MSNPs were able to affect endothelial functionality from outside the cells. These differences could be attributed to the different protein-corona composition of the MSNPs used, as suggested by sodium dodecyl sulfate polyacrylamide-gel electrophoresis analysis of the plasma proteins covering the MSNP surface. Moreover, doses of MSNPs up to 0.25 mg/mL perturbed network activity by increasing excitability, as detected by multielectrode-array technology, without affecting neuronal cell viability. Conclusion These results suggest that MSNPs may be low-risk if prepared with a diameter <30 nm and if they reach human tissues at doses <0.25 mg/mL. These important advances could help the rational design of NPs intended for biomedical uses, demonstrating that careful toxicity evaluation is necessary before using MSNPs in patients.

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Spontaneous coordinated activity in cultured networks: Analysis of multiple ignition sites, primary circuits, and burst phase delay distributions

Cited by 73 publications

References 38 publications

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

Quantitative examination of stimulus-response relations in cortical networks in vitro

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

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