Analysis of Cultured Neuronal Networks Using Intraburst Firing Characteristics

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.

[1]  G. Ramakers,et al.  Conditional firing probabilities in cultured neuronal networks: a stable underlying structure in widely varying spontaneous activity patterns , 2007, Journal of neural engineering.

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

[3]  R. Segev,et al.  Hidden neuronal correlations in cultured networks. , 2004, Physical review letters.

[4]  H. Robinson,et al.  Strengthening of synchronized activity by tetanic stimulation in cortical cultures: application of planar electrode arrays , 1998, IEEE Transactions on Biomedical Engineering.

[5]  Bruce Graham,et al.  Biologically plausible models of neurite outgrowth. , 2005, Progress in brain research.

[6]  Li I. Zhang,et al.  A critical window for cooperation and competition among developing retinotectal synapses , 1998, Nature.

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

[8]  A. Habets,et al.  Synaptogenesis in rat cerebral cortex cultures is affected during chronic blockade of spontaneous bioelectric activity by tetrodotoxin. , 1985, Brain research.

[9]  P. S. Wolters,et al.  Longterm stability and developmental changes in spontaneous network burst firing patterns in dissociated rat cerebral cortex cell cultures on multielectrode arrays , 2004, Neuroscience Letters.

[10]  Eshel Ben-Jacob,et al.  Functional holography of recorded neuronal networks activity , 2007, Neuroinformatics.

[11]  J. Roeper,et al.  Activity‐dependent formation of perforated synapses in cultured hippocampal neurons , 1999, The European journal of neuroscience.

[12]  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..

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

[14]  Bruce C Wheeler,et al.  Added astroglia promote greater synapse density and higher activity in neuronal networks. , 2007, Neuron glia biology.

[15]  W. J. Melssen,et al.  Detection and estimation of neural connectivity based on crosscorrelation analysis , 1987, Biological Cybernetics.

[16]  Yasuhiko Jimbo,et al.  Development of low magnesium-induced spontaneous synchronized bursting and GABAergic modulation in cultured rat neocortical neurons , 1996, Neuroscience Letters.

[17]  G J Brewer,et al.  Patterning to enhance activity of cultured neuronal networks. , 2004, IEE proceedings. Nanobiotechnology.

[18]  A. V. Ooyen,et al.  Effects of Inhibition on Neural Network Development Through Activity-dependent Neurite Outgrowth , 1997 .

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

[20]  W. Senn,et al.  Neocortical pyramidal cells respond as integrate-and-fire neurons to in vivo-like input currents. , 2003, Journal of neurophysiology.

[21]  A. van Ooyen,et al.  Effects of inhibition on neural network development through activity-dependent neurite outgrowth. , 1997, Journal of theoretical biology.

[22]  Shimon Marom,et al.  Learning in ex-vivo developing networks of cortical neurons. , 2005, Progress in brain research.

[23]  M. Corner,et al.  Implications of activity dependent neurite outgrowth for neuronal morphology and network development. , 1995, Journal of theoretical biology.

[24]  M Giugliano,et al.  Single-neuron discharge properties and network activity in dissociated cultures of neocortex. , 2004, Journal of neurophysiology.

[25]  John M. Beggs,et al.  Behavioral / Systems / Cognitive Neuronal Avalanches Are Diverse and Precise Activity Patterns That Are Stable for Many Hours in Cortical Slice Cultures , 2004 .

[26]  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.

[27]  A. V. Ooyen,et al.  Activity-dependent neurite outgrowth and neural network development. , 1994 .

[28]  Vincent Torre,et al.  Toward the neurocomputer: image Processing and pattern recognition with neuronal cultures , 2005, IEEE Transactions on Biomedical Engineering.

[29]  S.M. Potter,et al.  Spontaneous bursts are better indicators of tetanus-induced plasticity than responses to probe stimuli , 2005, Conference Proceedings. 2nd International IEEE EMBS Conference on Neural Engineering, 2005..

[30]  P. S. Wolters,et al.  Towards an improved serum-free, chemically defined medium for long-term culturing of cerebral cortex tissue , 1984, Neuroscience & Biobehavioral Reviews.

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

[32]  A. van Ooyen,et al.  Activity-dependent neurite outgrowth and neural network development. , 1994, Progress in brain research.

[33]  Steve M. Potter,et al.  Searching for plasticity in dissociated cortical cultures on multi-electrode arrays , 2006, Journal of Negative Results in BioMedicine.

[34]  Steve M. Potter,et al.  Controlling Bursting in Cortical Cultures with Closed-Loop Multi-Electrode Stimulation , 2005, The Journal of Neuroscience.

[35]  Daniel A. Wagenaar,et al.  Effects of random external background stimulation on network synaptic stability after tetanization , 2007, Neuroinformatics.

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

[37]  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.

[38]  Wim L. C. Rutten,et al.  Long-term characterization of firing dynamics of spontaneous bursts in cultured neural networks , 2004, IEEE Transactions on Biomedical Engineering.

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

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

[41]  Masahiro Kawahara,et al.  Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study , 1993, Neuroscience Research.

[42]  Shimon Marom,et al.  Selective Adaptation in Networks of Cortical Neurons , 2003, The Journal of Neuroscience.

[43]  H. Robinson,et al.  Modification of parallel activity elicited by propagating bursts in developing networks of rat cortical neurones , 1998, The European journal of neuroscience.

[44]  Yuji Ikegaya,et al.  Synfire Chains and Cortical Songs: Temporal Modules of Cortical Activity , 2004, Science.