Abstract
At early stages of development, neuronal cultures in vitro spontaneously reach a coherent state of collective firing in a pattern of nearly periodic global bursts. Although understanding the spontaneous activity of neuronal networks is of chief importance in neuroscience, the origin and nature of that pulsation has remained elusive. By combining high-resolution calcium imaging with modelling in silico, we show that this behaviour is controlled by the propagation of waves that nucleate randomly in a set of points that is specific to each culture and is selected by a non-trivial interplay between dynamics and topology. The phenomenon is explained by the noise focusing effect—a strong spatio-temporal localization of the noise dynamics that originates in the complex structure of avalanches of spontaneous activity. Results are relevant to neuronal tissues and to complex networks with integrate-and-fire dynamics and metric correlations, for instance, in rumour spreading on social networks.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bullmore, E. & Sporns, O. Complex brain networks: Graph theoretical analysis of structural and functional systems. Nature Rev. Neurosci. 10, 186–198 (2009).
Chialvo, D. R. Emergent complex neural dynamics. Nature Phys. 6, 744–750 (2010).
Spitzer, N. C. Electrical activity in early neuronal development. Nature 444, 707–712 (2006).
Blankenship, A. G. & Feller, M. B. Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nature Rev. Neurosci. 11, 18–29 (2010).
Buzsáki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004).
Sanchez-Vives, M. V. & McCormick, D. A. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nature Neurosci. 3, 1027–1034 (2000).
Ruiz-Mejias, M., Ciria-Suarez, L., Mattia, M. & Sanchez-Vives, M. V. Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse. J. Neurophysiol. 106, 2910–2921 (2011).
Soto, F., Ma, X., Cecil, J. L., Vo, B. Q., Culican, S. M. & Kerschensteiner, D. Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina. J. Neurosci. 32, 5426–5439 (2012).
Tscherter, A., Heuschkel, M. O., Renaud, P. & Streit, J. Spatiotemporal characterization of rhythmic activity in rat spinal cord slice cultures. Eur. J. Neurosci. 14, 179–190 (2001).
Eckmann, J-P., Feinerman, O., Gruendlinger, L., Moses, E., Soriano, J. & Tlusty, T. The physics of living neural networks. Phys. Rep. 449, 54–76 (2007).
Levina, A., Herrmann, J. M. & Geisel, T. Dynamical synapses causing self-organized criticality in neural networks. Nature Phys. 3, 857–860 (2007).
Soriano, J., Rodrı´guez Martı´nez, M., Tlusty, T. & Moses, E. Development of input connections in neural cultures. Proc. Natl Acad. Sci. USA 105, 13758–13763 (2008).
Feinerman, O., Rotem, A. & Moses, E. Reliable neuronal logic devices from patterned hippocampal cultures. Nature Phys. 4, 967–973 (2008).
Cohen, O., Keselman, A., Moses, E., Rodríguez Martínez, M., Soriano, J. & Tlusty, T. Quorum percolation in living neural networks. Europhys. Lett. 89, 18008 (2010).
Maeda, E., Robinson, H. P. & Kawana, A. The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons. J. Neurosci. 15, 6834–6845 (1995).
Opitz, T., de Lima, A. D. & Voigt, T. Spontaneous development of synchronous oscillatory activity during maturation of cortical networks in vitro. J. Neurophysiol. 88, 2196–2206 (2002).
Marom, S. & Shahaf, G. Development, learning and memory in large random networks of cortical neurons: Lessons beyond anatomy. Quart. Rev. Biophys. 35, 63–87 (2002).
Wagenaar, D. A., Pine, J. & Potter, S. M. An extremely rich repertoire of bursting patterns during the development of cortical cultures. BMC Neurosci. 7, 11 (2006).
Cohen, E., Ivenshitz, M., Amor-Baroukh, V., Greenberger, V. & Segal, M. Determinants of spontaneous activity in networks of cultured hippocampus. Brain Res. 1235, 21–30 (2008).
Ham, M. I., Bettencourt, L. M., McDaniel, F. D. & Gross, G. W. Spontaneous coordinated activity in cultured networks: Analysis of multiple ignition sites, primary circuits, and burst phase delay distributions. J. Comput. Neurosci. 24, 346–357 (2008).
Feinerman, O., Segal, M. & Moses, E. Identification and dynamics of spontaneous burst initiation zones in unidimensional neuronal cultures. J. Neurophysiol. 97, 2937–2948 (2007).
Eytan, D. & Marom, S. Dynamics and effective topology underlying synchronization in networks of cortical neurons. J. Neurosci. 26, 8465–8476 (2006).
Eckmann, J-P., Jacobi, S., Marom, S., Moses, E. & Zbinden, C. Leader neurons in population bursts of 2D living neural networks. New J. Phys. 10, 5011 (2008).
Eckmann, J-P., Moses, E., Stetter, O., Tlusty, T. & Zbinden, C. Leaders of neuronal cultures in a quorum percolation model. Front. Comput. Neurosci. 4, 132 (2010).
Segev, R., Baruchi, I., Hulata, E. & Ben-Jacob, E. Hidden neuronal correlations in cultured networks. Phys. Rev. Lett. 92, 118102 (2004).
Baruchi, I., Volman, V., Raichman, N., Shein, M. & Ben-Jacob, E. The emergence and properties of mutual synchronization in in vitro coupled cortical networks. Eur. J. Neurosci. 28, 1825–1835 (2008).
Tabak, J. & Latham, P. E. Analysis of spontaneous bursting activity in random neural networks. Neuroreport 14, 1445–1449 (2003).
Latham, P. E., Richmond, B. J., Nirenberg, S. & Nelson, P. G. Intrinsic dynamics in neuronal networks. II. Experiment. J. Neurophysiol. 83, 828–835 (2000).
Jacobi, S., Soriano, J. & Moses, E. BDNF and NT-3 increase velocity of activity front propagation in unidimensional hippocampal cultures. J. Neurophysiol. 104, 2932–2939 (2010).
Cohen, D. & Segal, M. Network bursts in hippocampal microcultures are terminated by exhaustion of vesicle pools. J. Neurophysiol. 106, 2314–2321 (2011).
Shein, M., Volman, V., Raichman, N., Hanein, Y. & Ben-Jacob, E. Management of synchronized network activity by highly active neurons. Phys. Biol. 5, 036008 (2008).
Izhikevich, E. M. Simple model of spiking neurons. IEEE Trans. Neural Netw. 14, 1569–1572 (2003).
Alvarez-Lacalle, E. & Moses, E. Slow and fast pulses in 1-D cultures of excitatory neurons. J. Comput. Neurosci. 26, 475–493 (2009).
Beggs, J. M. & Plenz, D. Neuronal avalanches in neocortical circuits. J. Neurosci. 23, 11167–11177 (2003).
Beggs, J. M. & Plenz, D. Neuronal avalanches are diverse and precise activity patterns that are stable for many hours in cortical slice cultures. J. Neurosci. 24, 5216–5229 (2004).
Mazzoni, A., Broccard, F. D., Garcia-Perez, E., Bonifazi, P., Ruaro, M. E. & Torre, V. On the dynamics of the spontaneous activity in neuronal networks. PLoS ONE 2, e439 (2007).
Tetzlaff, C., Okujeni, S., Egert, U., Wörgötter, F. & Butz, M. Self-organized criticality in developing neuronal networks. PLoS Comput. Biol. 6, e1001013 (2010).
Levina, A., Herrmann, J. M. & Geisel, T. Phase transitions towards criticality in a neural system with adaptive interactions. Phys. Rev. Lett. 102, 118110 (2009).
Millman, D., Mihalas, S., Kirkwood, A. & Niebur, E. Self-organized criticality occurs in non-conservative neuronal networks during ‘up’ states. Nature Phys. 6, 801–805 (2010).
Albert, R. & Barabási, A-L. Statistical mechanics of complex networks. Rev. Mod. Phys. 74, 47–97 (2002).
Tlusty, T. & Eckmann, J-P. Remarks on bootstrap percolation in metric networks. J. Phys. A 42, 205004 (2009).
Ito, S., Hansen, M. E., Heiland, R., Lumsdaine, A., Litke, A. M. & Beggs, J. M. Extending transfer entropy improves identification of effective connectivity in a spiking cortical network model. PLoS ONE 6, e27431 (2011).
Stetter, O., Battaglia, D., Soriano, J. & Geisel, T. Model-free reconstruction of excitatory neuronal connectivity from calcium imaging signals. PLoS Comput. Biol. 8, e1002653 (2012).
Moons, W. G., Mackie, D. M. & Garcia-Marques, T. The impact of repetition-induced familiarity on agreement with weak and strong arguments. J. Pers. Soc. Psychol. 96, 32–44 (2009).
Kitsak, M., Gallos, L. K., Havlin, S., Liljeros, F., Muchnik, L., Stanley, H. E. & Makse, H. A. Identification of influential spreaders in complex networks. Nature Phys. 6, 888–893 (2010).
Fagiolo, G. Clustering in complex directed networks. Phys. Rev. E 76, 26107 (2007).
Bastian, M., Heymann, S. & Jacomy, M. Gephi: An open source software for exploring and manipulating networks. Int. AAAI Conf. on Weblogs and Social Media (2009).
Golomb, D. & Amitai, Y. Propagating neuronal discharges in neocortical slices: computational and experimental study. J. Neurophysiol. 78, 1199–1211 (1997).
Tsodyks, M. V. & Markram, H. The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc. Natl Acad. Sci. USA 94, 719–723 (1997).
Blondel, V. D., Guillaume, J-L., Lambiotte, R. & Lefebvre, E. Fast unfolding of communities in large networks. J. Stat. Mech. 10, 008 (2008).
Acknowledgements
We thank T. Tlusty, E. Moses, and M.V. Sánchez-Vives for fruitful discussions. We acknowledge financial support from Ministerio de Ciencia e Innovación (Spain) under projects FIS2009-07523, and FIS2010-21924-C02-02, FIS2011-28820-C02-01 and the Generalitat de Catalunya under project 2009-SGR-00014.
Author information
Authors and Affiliations
Contributions
J.G.O. developed the model in silico, and performed the numerical simulations and data analysis. J.S. conceived and designed the experiments. J.G.O. and E.A-L. conceived the model in silico. J.S. and S.T. performed the experiments and analysed experimental data. J.G.O., E.A-L. and J.C. contributed to the theoretical analysis. J.C. developed analytical tools and the conceptual framework. All authors contributed to data interpretation and wrote the manuscript. J.S. and J.C. supervised the project.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary Information (PDF 2895 kb)
Supplementary Movie
Supplementary Movie 1 (AVI 29201 kb)
Supplementary Movie
Supplementary Movie 2 (AVI 12296 kb)
Supplementary Movie
Supplementary Movie 3 (AVI 11015 kb)
Supplementary Movie
Supplementary Movie 4 (AVI 6679 kb)
Supplementary Movie
Supplementary Movie 5 (AVI 985 kb)
Supplementary Movie
Supplementary Movie 6 (AVI 8860 kb)
Rights and permissions
About this article
Cite this article
Orlandi, J., Soriano, J., Alvarez-Lacalle, E. et al. Noise focusing and the emergence of coherent activity in neuronal cultures. Nature Phys 9, 582–590 (2013). https://doi.org/10.1038/nphys2686
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nphys2686
This article is cited by
-
Parkinson’s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration
npj Parkinson's Disease (2021)
-
Single-neuron dynamical effects of dendritic pruning implicated in aging and neurodegeneration: towards a measure of neuronal reserve
Scientific Reports (2021)
-
Box scaling as a proxy of finite size correlations
Scientific Reports (2021)
-
A novel methodology to describe neuronal networks activity reveals spatiotemporal recruitment dynamics of synchronous bursting states
Journal of Computational Neuroscience (2021)
-
Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington’s disease
BMC Biology (2020)