Emergence of a Small-World Functional Network in Cultured Neurons

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.

[1]  Michael I. Ham,et al.  Functional structure of cortical neuronal networks grown in vitro. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  Cees van Leeuwen,et al.  Robust emergence of small-world structure in networks of spiking neurons , 2007, Cognitive Neurodynamics.

[3]  C. Stam,et al.  Small-world networks and functional connectivity in Alzheimer's disease. , 2006, Cerebral cortex.

[4]  Olaf Sporns,et al.  Symbiotic relationship between brain structure and dynamics , 2009, BMC Neuroscience.

[5]  E. Wanke,et al.  Short-latency cross- and autocorrelation identify clusters of interacting cortical neurons recorded from multi-electrode array , 2009, Journal of Neuroscience Methods.

[6]  Andreas Daffertshofer,et al.  Comparing Brain Networks of Different Size and Connectivity Density Using Graph Theory , 2010, PloS one.

[7]  Yong He,et al.  Disrupted small-world networks in schizophrenia. , 2008, Brain : a journal of neurology.

[8]  P. Massobrio,et al.  Network plasticity in cortical assemblies , 2008, The European journal of neuroscience.

[9]  Larry Bull,et al.  Towards Neuronal Computing: Simple Creation of Two Logic Functions in 3D Cell Cultures using Multi-Electrode Arrays , 2008, Int. J. Unconv. Comput..

[10]  D. Watts The “New” Science of Networks , 2004 .

[11]  C Cherniak,et al.  Component placement optimization in the brain , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  Alessandro Vato,et al.  Dissociated cortical networks show spontaneously correlated activity patterns during in vitro development , 2006, Brain Research.

[13]  M. Corner,et al.  Dynamics and plasticity in developing neuronal networks in vitro. , 2005, Progress in brain research.

[14]  Danny Eytan,et al.  Dynamics and Effective Topology Underlying Synchronization in Networks of Cortical Neurons , 2006, The Journal of Neuroscience.

[15]  Sharon L. Milgram,et al.  The Small World Problem , 1967 .

[16]  W. M. van der Flier,et al.  Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory , 2009, BMC Neuroscience.

[17]  Vito Latora,et al.  Complex Networks: New Trends for the Analysis of Brain Connectivity , 2010, Int. J. Bifurc. Chaos.

[18]  Slawomir J. Nasuto,et al.  Controlling a mobile robot with a biological brain , 2010 .

[19]  Slawomir J. Nasuto,et al.  Robust methodology for the study of cultured neuronal networks On MEAs , 2008 .

[20]  Simon W. Moore,et al.  Efficient Physical Embedding of Topologically Complex Information Processing Networks in Brains and Computer Circuits , 2010, PLoS Comput. Biol..

[21]  Sergio Martinoia,et al.  Connecting Neurons to a Mobile Robot: An In Vitro Bidirectional Neural Interface , 2007, Comput. Intell. Neurosci..

[22]  Sujit K Sikdar,et al.  Small‐world network topology of hippocampal neuronal network is lost, in an in vitro glutamate injury model of epilepsy , 2007, The European journal of neuroscience.

[23]  R. Baughman,et al.  Primary culture of identified neurons from the visual cortex of postnatal rats , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  Piskorski Jakub,et al.  Mining Massive Data Sets for Security , 2008 .

[25]  Amir Ayali,et al.  Contextual regularity and complexity of neuronal activity: From stand-alone cultures to task-performing animals , 2004, Complex..

[26]  Shan Yu,et al.  A Small World of Neuronal Synchrony , 2008, Cerebral cortex.

[27]  Edward T. Bullmore,et al.  Efficiency and Cost of Economical Brain Functional Networks , 2007, PLoS Comput. Biol..

[28]  V Latora,et al.  Efficient behavior of small-world networks. , 2001, Physical review letters.

[29]  Linda Douw,et al.  Human Neuroscience , 2022 .

[30]  K. Gurney,et al.  Network ‘Small-World-Ness’: A Quantitative Method for Determining Canonical Network Equivalence , 2008, PloS one.

[31]  Slawomir J. Nasuto,et al.  Architecture for Neuronal Cell Control of a Mobile Robot , 2008, EUROS.

[32]  E. Bullmore,et al.  A Resilient, Low-Frequency, Small-World Human Brain Functional Network with Highly Connected Association Cortical Hubs , 2006, The Journal of Neuroscience.

[33]  O. Sporns,et al.  Organization, development and function of complex brain networks , 2004, Trends in Cognitive Sciences.

[34]  Steve M. Potter,et al.  A new approach to neural cell culture for long-term studies , 2001, Journal of Neuroscience Methods.

[35]  E. Bullmore,et al.  Adaptive reconfiguration of fractal small-world human brain functional networks , 2006, Proceedings of the National Academy of Sciences.

[36]  Rodrigo Quian Quiroga,et al.  Nonlinear multivariate analysis of neurophysiological signals , 2005, Progress in Neurobiology.

[37]  J. J. Wright,et al.  Attractor Dynamics and Thermodynamic Analogies in the Cerebral Cortex: Synchronous Oscillation, the Background EEG, and the Regulation of Attention , 2011, Bulletin of mathematical biology.

[38]  Scott T. Grafton,et al.  Dynamic reconfiguration of human brain networks during learning , 2010, Proceedings of the National Academy of Sciences.

[39]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[40]  G Shahaf,et al.  Learning in Networks of Cortical Neurons , 2001, The Journal of Neuroscience.

[41]  Slawomir J. Nasuto,et al.  Multiscale Evolving Complex Network Model of Functional Connectivity in Neuronal Cultures , 2012, IEEE Transactions on Biomedical Engineering.

[42]  Danny Eytan,et al.  Order-Based Representation in Random Networks of Cortical Neurons , 2008, PLoS Comput. Biol..

[43]  Luís M. A. Bettencourt,et al.  Spontaneous coordinated activity in cultured networks: Analysis of multiple ignition sites, primary circuits, and burst phase delay distributions , 2008, Journal of Computational Neuroscience.

[44]  Bill Doult,et al.  On with the new. , 1996, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[45]  Steve M. Potter,et al.  Spatio-temporal electrical stimuli shape behavior of an embodied cortical network in a goal-directed learning task , 2008, Journal of neural engineering.

[46]  O. Sporns,et al.  Identification and Classification of Hubs in Brain Networks , 2007, PloS one.

[47]  M. Corner,et al.  Activity-dependent plasticity of inhibitory and excitatory amino acid transmitter systems in cultured rat cerebral cortex , 1994, International Journal of Developmental Neuroscience.

[48]  Aviva Petrie,et al.  T testing the immune system. , 2008, Immunity.

[49]  Shimon Marom,et al.  Development, learning and memory in large random networks of cortical neurons: lessons beyond anatomy , 2002, Quarterly Reviews of Biophysics.

[50]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[51]  Albert-László Barabási,et al.  Error and attack tolerance of complex networks , 2000, Nature.

[52]  G. Buzsáki,et al.  Interneuron Diversity series: Circuit complexity and axon wiring economy of cortical interneurons , 2004, Trends in Neurosciences.

[53]  Arjen van Ooyen,et al.  Low-frequency stimulation induces stable transitions in stereotypical activity in cortical networks. , 2008, Biophysical journal.

[54]  J. Ball,et al.  Statistics review 4: Sample size calculations , 2002, Critical care.

[55]  Amir Ayali,et al.  Morphological characterization of in vitro neuronal networks. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[56]  T.B. DeMarse,et al.  MeaBench: A toolset for multi-electrode data acquisition and on-line analysis , 2005, Conference Proceedings. 2nd International IEEE EMBS Conference on Neural Engineering, 2005..

[57]  Michel A. Picardo,et al.  GABAergic Hub Neurons Orchestrate Synchrony in Developing Hippocampal Networks , 2009, Science.

[58]  S. Strogatz Exploring complex networks , 2001, Nature.

[59]  H E Stanley,et al.  Classes of small-world networks. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  H. Robinson,et al.  Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons. , 1999, Biophysical journal.

[61]  Olaf Sporns,et al.  Network structure of cerebral cortex shapes functional connectivity on multiple time scales , 2007, Proceedings of the National Academy of Sciences.

[62]  H. Robinson,et al.  The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[63]  H. Robinson,et al.  Spontaneous periodic synchronized bursting during formation of mature patterns of connections in cortical cultures , 1996, Neuroscience Letters.

[64]  M. Corner,et al.  Physiological effects of sustained blockade of excitatory synaptic transmission on spontaneously active developing neuronal networks—an inquiry into the reciprocal linkage between intrinsic biorhythms and neuroplasticity in early ontogeny , 2002, Neuroscience & Biobehavioral Reviews.

[65]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[66]  Steve M. Potter,et al.  An extremely rich repertoire of bursting patterns during the development of cortical cultures , 2006, BMC Neuroscience.

[67]  J. Lawrence,et al.  Cholinergic control of GABA release: emerging parallels between neocortex and hippocampus , 2008, Trends in Neurosciences.

[68]  Mark E. J. Newman,et al.  The Structure and Function of Complex Networks , 2003, SIAM Rev..

[69]  Jan Stegenga,et al.  The Effect of Slow Electrical Stimuli to Achieve Learning in Cultured Networks of Rat Cortical Neurons , 2010, PloS one.

[70]  T. Voigt,et al.  Activation of Early Silent Synapses by Spontaneous Synchronous Network Activity Limits the Range of Neocortical Connections , 2005, The Journal of Neuroscience.

[71]  Slawomir J. Nasuto,et al.  A novel approach to the detection of synchronisation in EEG based on empirical mode decomposition , 2007, Journal of Computational Neuroscience.

[72]  S. Cerutti,et al.  Statistical Long-Term Correlations in Dissociated Cortical Neuron Recordings , 2009, IEEE Transactions on Neural Systems and Rehabilitation Engineering.