Modularity Induced Gating and Delays in Neuronal Networks

Neural networks, despite their highly interconnected nature, exhibit distinctly localized and gated activation. Modularity, a distinctive feature of neural networks, has been recently proposed as an important parameter determining the manner by which networks support activity propagation. Here we use an engineered biological model, consisting of engineered rat cortical neurons, to study the role of modular topology in gating the activity between cell populations. We show that pairs of connected modules support conditional propagation (transmitting stronger bursts with higher probability), long delays and propagation asymmetry. Moreover, large modular networks manifest diverse patterns of both local and global activation. Blocking inhibition decreased activity diversity and replaced it with highly consistent transmission patterns. By independently controlling modularity and disinhibition, experimentally and in a model, we pose that modular topology is an important parameter affecting activation localization and is instrumental for population-level gating by disinhibition.

[1]  L.F. Abbott,et al.  Gating Multiple Signals through Detailed Balance of Excitation and Inhibition in Spiking Networks , 2009, Nature Neuroscience.

[2]  V. Mountcastle The columnar organization of the neocortex. , 1997, Brain : a journal of neurology.

[3]  J Martinerie,et al.  Functional modularity of background activities in normal and epileptic brain networks. , 2008, Physical review letters.

[4]  M. Brecht,et al.  Grid-Layout and Theta-Modulation of Layer 2 Pyramidal Neurons in Medial Entorhinal Cortex , 2014, Science.

[5]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[6]  Idan Segev,et al.  On the Transmission of Rate Code in Long Feedforward Networks with Excitatory–Inhibitory Balance , 2003, The Journal of Neuroscience.

[7]  J J Jack,et al.  The effects of synaptic noise on measurements of evoked excitatory postsynaptic response amplitudes. , 1997, Biophysical journal.

[8]  L. Abbott,et al.  Synaptic computation , 2004, Nature.

[9]  Shilpa Chakravartula,et al.  Complex Networks: Structure and Dynamics , 2014 .

[10]  Yong-Yeol Ahn,et al.  Topological Cluster Analysis Reveals the Systemic Organization of the Caenorhabditis elegans Connectome , 2011, PLoS Comput. Biol..

[11]  H. Markram,et al.  t Synchrony Generation in Recurrent Networks with Frequency-Dependent Synapses , 2000, The Journal of Neuroscience.

[12]  D Kleinfeld,et al.  Controlled outgrowth of dissociated neurons on patterned substrates , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  Edward T. Bullmore,et al.  Modular and Hierarchically Modular Organization of Brain Networks , 2010, Front. Neurosci..

[14]  Marcus Kaiser,et al.  Clustered organization of cortical connectivity , 2007, Neuroinformatics.

[15]  Lief E. Fenno,et al.  Neocortical excitation/inhibition balance in information processing and social dysfunction , 2011, Nature.

[16]  Eshel Ben-Jacob,et al.  Generative modelling of regulated dynamical behavior in cultured neuronal networks , 2004 .

[17]  Eshel Ben-Jacob,et al.  Innate Synchronous Oscillations in Freely-Organized Small Neuronal Circuits , 2010, PloS one.

[18]  B. Rudy,et al.  Perisomatic GABA Release and Thalamocortical Integration onto Neocortical Excitatory Cells Are Regulated by Neuromodulators , 2008, Neuron.

[19]  Massimo Avoli,et al.  GABA and Epileptogenesis , 1997, Epilepsia.

[20]  Marcus Kaiser,et al.  Optimal Hierarchical Modular Topologies for Producing Limited Sustained Activation of Neural Networks , 2009, Front. Neuroinform..

[21]  S. Sherman Tonic and burst firing: dual modes of thalamocortical relay , 2001, Trends in Neurosciences.

[22]  E. Ben-Jacob,et al.  The emergence and properties of mutual synchronization in in vitro coupled cortical networks , 2008, The European journal of neuroscience.

[23]  Marcus Kaiser,et al.  Criticality of spreading dynamics in hierarchical cluster networks without inhibition , 2007, 0802.2508.

[24]  D. Contreras,et al.  Impaired Fast-Spiking, Suppressed Cortical Inhibition, and Increased Susceptibility to Seizures in Mice Lacking Kv3.2 K+ Channel Proteins , 2000, The Journal of Neuroscience.

[25]  T. Sejnowski,et al.  Synchrony of Thalamocortical Inputs Maximizes Cortical Reliability , 2010, Science.

[26]  T. A. Ryan,et al.  Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system , 2000, Nature Cell Biology.

[27]  M. Shanahan Metastable chimera states in community-structured oscillator networks. , 2009, Chaos.

[28]  Luca Berdondini,et al.  A microelectrode array (MEA) integrated with clustering structures for investigating in vitro neurodynamics in confined interconnected sub-populations of neurons , 2006 .

[29]  Niraj S. Desai,et al.  Plasticity in the intrinsic excitability of cortical pyramidal neurons , 1999, Nature Neuroscience.

[30]  T. A. Ryan,et al.  The efficiency of the synaptic vesicle cycle at central nervous system synapses. , 2006, Trends in cell biology.

[31]  E. Ben-Jacob,et al.  Engineered neuronal circuits shaped and interfaced with carbon nanotube microelectrode arrays , 2009, Biomedical microdevices.

[32]  D. Buxhoeveden,et al.  The minicolumn hypothesis in neuroscience. , 2002, Brain : a journal of neurology.

[33]  Ronen Segev,et al.  Formation of electrically active clusterized neural networks. , 2003, Physical review letters.

[34]  Gaute T. Einevoll,et al.  Estimation of population firing rates and current source densities from laminar electrode recordings , 2008, Journal of Computational Neuroscience.

[35]  Olaf Sporns,et al.  Connectivity and complexity: the relationship between neuroanatomy and brain dynamics , 2000, Neural Networks.

[36]  G. Turrigiano Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same , 1999, Trends in Neurosciences.

[37]  Shimon Marom,et al.  Enhancement of neural representation capacity by modular architecture in networks of cortical neurons , 2012, The European journal of neuroscience.

[38]  E Ben-Jacob,et al.  Compact self-wiring in cultured neural networks , 2006, Journal of neural engineering.

[39]  Rick Dale,et al.  Assessing bimodality to detect the presence of a dual cognitive process , 2013, Behavior research methods.

[40]  Joaquín J. Torres,et al.  Robust Short-Term Memory without Synaptic Learning , 2010, PloS one.

[41]  Eshel Ben-Jacob,et al.  Engineered Neuronal Circuits: A New Platform for Studying the Role of Modular Topology , 2011, Front. Neuroeng..

[42]  B. Katz,et al.  Spontaneous subthreshold activity at motor nerve endings , 1952, The Journal of physiology.

[43]  S. Goldring,et al.  Surgical management of epilepsy using epidural recordings to localize the seizure focus. Review of 100 cases. , 1984, Journal of neurosurgery.

[44]  Idan Segev,et al.  Methods in Neuronal Modeling , 1988 .

[45]  Theo Geisel,et al.  Model-Free Reconstruction of Excitatory Neuronal Connectivity from Calcium Imaging Signals , 2012, PLoS Comput. Biol..

[46]  Sergio Gómez,et al.  Emergence of Assortative Mixing between Clusters of Cultured Neurons , 2014, PLoS Comput. Biol..

[47]  Alan C. Evans,et al.  Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography. , 2009, Cerebral cortex.

[48]  D. Plenz,et al.  The organizing principles of neuronal avalanches: cell assemblies in the cortex? , 2007, Trends in Neurosciences.

[49]  P. Somogyi A specific ‘axo-axonal’ interneuron in the visual cortex of the rat , 1977, Brain Research.

[50]  D. Long Networks of the Brain , 2011 .

[51]  W. Newsome,et al.  The Variable Discharge of Cortical Neurons: Implications for Connectivity, Computation, and Information Coding , 1998, The Journal of Neuroscience.

[52]  Raj Kumar Pan,et al.  Modularity produces small-world networks with dynamical time-scale separation , 2008, 0802.3671.

[53]  Donald E Ingber,et al.  Synaptic Reorganization in Scaled Networks of Controlled Size , 2007, The Journal of Neuroscience.

[54]  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.

[55]  J. Martinerie,et al.  The brainweb: Phase synchronization and large-scale integration , 2001, Nature Reviews Neuroscience.

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

[57]  Michael Rudolph,et al.  Note on “ Characterization of subthreshold voltage fluctuations in neuronal membranes ” , 2008 .

[58]  Eshel Ben-Jacob,et al.  Calcium and synaptic dynamics underlying reverberatory activity in neuronal networks , 2007, Physical biology.

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

[60]  Jaume Casademunt,et al.  Noise focusing and the emergence of coherent activity in neuronal cultures , 2013, Nature Physics.

[61]  Jürg Streit,et al.  Patterns of spontaneous activity in unstructured and minimally structured spinal networks in culture , 2005, Experimental Brain Research.

[62]  Marcus Kaiser,et al.  Brain architecture: a design for natural computation , 2007, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[63]  A. Litwin-Kumar,et al.  Slow dynamics and high variability in balanced cortical networks with clustered connections , 2012, Nature Neuroscience.

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

[65]  R. Yuste,et al.  The Brain Activity Map Project and the Challenge of Functional Connectomics , 2012, Neuron.

[66]  G. Ermentrout,et al.  Analysis of neural excitability and oscillations , 1989 .

[67]  M. Scanziani,et al.  How Inhibition Shapes Cortical Activity , 2011, Neuron.

[68]  Ad Aertsen,et al.  Gating of Signal Propagation in Spiking Neural Networks by Balanced and Correlated Excitation and Inhibition , 2010, The Journal of Neuroscience.

[69]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[70]  Henrike Planert,et al.  Target Selectivity of Feedforward Inhibition by Striatal Fast-Spiking Interneurons , 2013, The Journal of Neuroscience.

[71]  M. Shanahan Dynamical complexity in small-world networks of spiking neurons. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[72]  Bruce C Wheeler,et al.  Propagation of action potential activity in a predefined microtunnel neural network , 2011, Journal of neural engineering.

[73]  A. Aertsen,et al.  Spiking activity propagation in neuronal networks: reconciling different perspectives on neural coding , 2010, Nature Reviews Neuroscience.

[74]  E. Ben-Jacob,et al.  Management of synchronized network activity by highly active neurons , 2008, Physical biology.

[75]  Y. Ben-Ari Developing networks play a similar melody , 2001, Trends in Neurosciences.