Multiscale Evolving Complex Network Model of Functional Connectivity in Neuronal Cultures

Spencer, Matthew; Downes, Julia; Xydas, Dimitris; Hammond, Mark W.; Becerra, Victor M.; Warwick, Kevin; Whalley, Ben; Nasuto, Slawomir J.

doi:10.1109/tbme.2011.2171340

Cited by 12 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, a change in the culture's spontaneous activity patterns could drive the topology transformation. Results herein and in [61] suggest that once the topology of the network has emerged, equilibrium states may exist at different time scales - from transient synchronization between subgroups of neural units at the short time-scale to regular occurrence of such transiently activated subgroups over longer time-scales. Modeling studies may provide further insight into the role of synchronization and the evolution of such equilibrium states [62] , whilst pharmacological manipulation of specific neuron sub-types could verify biological mechanisms behind activity modulation.…”

Section: Discussionmentioning

confidence: 74%

Emergence of a Small-World Functional Network in Cultured Neurons

et al. 2012

View full text Add to dashboard Cite

The functional networks of cultured neurons exhibit complex network properties similar to those found in vivo. Starting from random seeding, cultures undergo significant reorganization during the initial period in vitro, yet despite providing an ideal platform for observing developmental changes in neuronal connectivity, little is known about how a complex functional network evolves from isolated neurons. In the present study, evolution of functional connectivity was estimated from correlations of spontaneous activity. Network properties were quantified using complex measures from graph theory and used to compare cultures at different stages of development during the first 5 weeks in vitro. Networks obtained from young cultures (14 days in vitro) exhibited a random topology, which evolved to a small-world topology during maturation. The topology change was accompanied by an increased presence of highly connected areas (hubs) and network efficiency increased with age. The small-world topology balances integration of network areas with segregation of specialized processing units. The emergence of such network structure in cultured neurons, despite a lack of external input, points to complex intrinsic biological mechanisms. Moreover, the functional network of cultures at mature ages is efficient and highly suited to complex processing tasks.

show abstract

Section: Discussionmentioning

confidence: 74%

Emergence of a Small-World Functional Network in Cultured Neurons

et al. 2012

View full text Add to dashboard Cite

show abstract

“…All have relied upon ICC markers and single‐electrode patch‐clamp electrophysiology to demonstrate and assess a neuronal phenotype; yet a key feature of neuronal tissue is the presence of spontaneous bioelectrical activity arising from highly connected networks. The activity of these networks can be monitored by culturing them directly onto tools such as MEAs (Downes et al ., ; Hammond et al ., ; Rolston et al ., ; Spencer et al ., ; Wagenaar et al ., , ), but the protracted differentiation and maturation periods required by stem cell populations, prior to forming functional networks, and the high per unit cost of MEAs make this approach low‐throughput and costly. Here we have shown that functional neuronal networks can be cultured in inert 3D membranes and that their spontaneous activity can be monitored via MEA.…”

Section: Discussionmentioning

confidence: 99%

Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks

Smith

Silveirinha

Stein

et al. 2015

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

“…Poli and coworkers have summarized a series of approaches that can be used to analyze network connectivity using MEA recordings and suggested a holistic approach can be useful in identifying unique topological properties of neuronal networks that emerge from the interactions amongst different nodes [ 99 ]. Spencer and coworkers have used modeling approaches that use the multiple scale of in vitro neuronal networks in order to derive functional measurements indicative of sequential dynamics and synchronization [ 100 ]. In general, the analyses of network activity measured with MEA can benefit from these multilevel and modeling approaches.…”

Section: Expanding the Mea Analysis Toolkit In Ipsc Disease Modelingmentioning

confidence: 99%

Multielectrode Arrays for Functional Phenotyping of Neurons from Induced Pluripotent Stem Cell Models of Neurodevelopmental Disorders

McCready

Gordillo-Sampedro

Pradeepan

et al. 2022

Biology

View full text Add to dashboard Cite

In vitro multielectrode array (MEA) systems are increasingly used as higher-throughput platforms for functional phenotyping studies of neurons in induced pluripotent stem cell (iPSC) disease models. While MEA systems generate large amounts of spatiotemporal activity data from networks of iPSC-derived neurons, the downstream analysis and interpretation of such high-dimensional data often pose a significant challenge to researchers. In this review, we examine how MEA technology is currently deployed in iPSC modeling studies of neurodevelopmental disorders. We first highlight the strengths of in vitro MEA technology by reviewing the history of its development and the original scientific questions MEAs were intended to answer. Methods of generating patient iPSC-derived neurons and astrocytes for MEA co-cultures are summarized. We then discuss challenges associated with MEA data analysis in a disease modeling context, and present novel computational methods used to better interpret network phenotyping data. We end by suggesting best practices for presenting MEA data in research publications, and propose that the creation of a public MEA data repository to enable collaborative data sharing would be of great benefit to the iPSC disease modeling community.

show abstract

Multiscale Evolving Complex Network Model of Functional Connectivity in Neuronal Cultures

Cited by 12 publications

References 19 publications

Emergence of a Small-World Functional Network in Cultured Neurons

Emergence of a Small-World Functional Network in Cultured Neurons

Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks

Multielectrode Arrays for Functional Phenotyping of Neurons from Induced Pluripotent Stem Cell Models of Neurodevelopmental Disorders

Contact Info

Product

Resources

About