The role of network architecture in the onset of spontaneous activity

  • Diletta Pozzi Department of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, USA; Neurobiology Sector, International School for Advanced Studies (SISSA), Italy
  • Nicolò Meneghetti Computational Neuroengineering Lab, The Biorobotics Institute, Scuola Superiore Sant'Anna, Italy
  • Anjan Roy Abdus Salam International Center for Theoretical Physics (ICTP), Italy
  • Beatrice Pastore Neurobiology Sector, International School for Advanced Studies (SISSA), Italy
  • Alberto Mazzoni Computational Neuroengineering Lab, The Biorobotics Institute, Scuola Superiore Sant'Anna, Italy
  • Matteo Marsili Abdus Salam International Center for Theoretical Physics (ICTP), Italy
  • Vincent Torre Neurobiology Sector, International School for Advanced Studies (SISSA), Italy; Cixi Institute of Biomedical Engineering (CNITECH), Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, China; Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou Institute of Systems Medicine (ISM), China
Keywords: Neuronal network, Calcium imaging, GABAergic neuron, Power law, Neural model


BACKGROUND: The spontaneous activity of neuronal networks has been studied in in vitro models such as brain slices and dissociated cultures. However, a comparison between their dynamical properties in these two types of biological samples is still missing and it would clarify the role of architecture in shaping networks’ operation.

METHODS: We used calcium imaging to identify clusters of neurons co-activated in hippocampal and cortical slices, as well as in dissociated neuronal cultures, from GAD67-GFP mice. We used statistical tests, power law fitting and neural modelling to characterize the spontaneous events observed.

RESULTS:  In slices, we observed intermittency between silent periods, the appearance of Confined Optical Transients (COTs) and of Diffused Optical Transients (DOTs). DOTs in the cortex were preferentially triggered by the activity of neurons located in layer III-IV, poorly coincident with GABAergic neurons. DOTs had a duration of 10.2±0.3 and 8.2±0.4 seconds in cortical and hippocampal slices, respectively, and were blocked by tetrodotoxin, indicating their neuronal origin. The amplitude and duration of DOTs were controlled by NMDA and GABA-A receptors. In dissociated cultures, we observed an increased synchrony in GABAergic neurons and the presence of global synchronous events similar to DOTs, but with a duration shorter than that seen in the native tissues.

CONCLUSION: We conclude that DOTs are shaped by the network architecture and by the balance between inhibition and excitation, and that they can be reproduced by network models with a minimal number of parameters.


Faisal AA, Selen LPJ, Wolpert DM. Noise in the nervous system. Nat Rev Neurosci. 2008 Apr;9(4):292-303.

Luczak A, Barthó P, Marguet SL, Buzsáki G, Harris KD. Sequential structure of neocortical spontaneous activity in vivo. Proc Natl Acad Sci USA. 2007 Jan 2;104(1):347-52.

Steriade M, Nuñez A, Amzica F. A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci. 1993 Aug;13(8):3252-65.

Timofeev I, Grenier F, Steriade M. Disfacilitation and active inhibition in the neocortex during the naturalsleep-wake cycle: an intracellular study. Proc Natl Acad Sci USA. 2001 Feb 13;98(4):1924-9.

Petersen CCH, Grinvald A, Sakmann B. Spatiotemporal dynamics of sensory responses in layer 2/3 of rat barrel cortex measured in vivo by voltage-sensitive dye imaging combined with whole-cell voltage recordings and neuron reconstructions. J Neurosci. 2003 Feb 15;23(4):1298-309.

Sachidhanandam S, Sreenivasan V, Kyriakatos A, Kremer Y, Petersen CCH. Membrane potential correlates of sensory perception in mouse barrel cortex. Nat Neurosci. 2013 Nov;16(11):1671-7.

Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G. Local sleep in awake rats. Nature. 2011 Apr;472(7344):443-7.

Engel TA, Steinmetz NA, Gieselmann MA, Thiele A, Moore T, Boahen K. Selective modulation of cortical state during spatial attention. Science. 2016 02;354(6316):1140-4.

Timofeev I, Grenier F, Bazhenov M, Sejnowski TJ, Steriade M. Origin of slow cortical oscillations in deafferented cortical slabs. Cereb Cortex N Y N 1991. 2000 Dec;10(12):1185-99.

Sanchez-Vives MV, McCormick DA. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci. 2000 Oct;3(10):1027-34.

Fanselow EE, Connors BW. The roles of somatostatin-expressing (GIN) and fast-spiking inhibitory interneurons in UP-DOWN states of mouse neocortex. J Neurophysiol. 2010Aug;104(2):596-606.

Compte A, Reig R, Descalzo VF, Harvey MA, Puccini GD, Sanchez-Vives MV. Spontaneous high-frequency (10-80 Hz) oscillations during up states in the cerebral cortex in vitro. J Neurosci. 2008 Dec 17;28(51):13828-44.

Buzsáki G. Theta oscillations in the hippocampus. Neuron. 2002 Jan;33(3):325-40.

Sirota A, Buzsáki G. Interaction between neocortical and hippocampal networks via slow oscillations. Thalamus Relat Syst. 2005 Dec;3(04):245.

Markram H, Muller E, Ramaswamy S, Reimann MW, Abdellah M, Sanchez CA, et al. Reconstruction and simulation of neocortical microcircuitry. Cell. 2015 Oct;163(2):456-92.

Scarpetta S, de Candia A. Alternation of up and down states at a dynamical phase-transition of a neural network with spatiotemporal attractors. Front Syst Neurosci [Internet]. 2014 May 19;8:88.

Curto C, Sakata S, Marguet S, Itskov V, Harris KD. A simple model of cortical dynamics explains variability and state dependence of sensory responses in urethane-anesthetized auditory cortex. J Neurosci. 2009 Aug 26;29(34):10600-12.

Goodfellow M, Glendinning P. Mechanisms of intermittent state transitions in a coupled heterogeneous oscillator model of epilepsy. J Math Neurosci. 2013 Aug 14;3:17.

Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J-I, Obata K, Kaneko T. Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol. 2003 Dec 1;467(1):60-79.

Cossart R, Ikegaya Y, Yuste R. Calcium imaging of cortical networks dynamics. Cell Calcium. 2005 May;37(5):451-7.

Yang W, Yuste R. In vivo imaging of neural activity. Nat Methods. 2017 Mar 31;14(4):349-59.

Gähwiler BH, Capogna M, Debanne D, McKinney RA, Thompson SM. Organotypic slice cultures: a technique has come of age. Trends Neurosci. 1997 Oct;20(10):471-7.

Stoppini L, Buchs PA, Muller D. A simple method for organotypic cultures of nervous tissue. J Neurosci Methods. 1991 Apr;37(2):173-82.

Clauset A, Shalizi C, Newman M. Power-Law Distributions in Empirical Data. SIAM Rev. 2009 Nov 4;51(4):661-703.

Regad T, Bellodi C, Nicotera P, Salomoni P. The tumor suppressor Pml regulates cell fate in the developing neocortex. Nat Neurosci. 2009 Feb;12(2):132-40.

Douglas RJ, Martin KAC. Neuronal circuits of the neocortex. Annu Rev Neurosci. 2004;27:419-51.

Narahashi T, Moore JW, Scott WR. Tetrodotoxin Blockage of Sodium Conductance Increase in Lobster Giant Axons. J Gen Physiol. 1964 May 1;47(5):965-74.

Gilbride CJ. The hyperexcitability of dentate granule neurons in organotypic hippocampal slice cultures is due to reorganization of synaptic inputs in vitro. Physiol Rep. 2016 Oct 1;4(19):n/a-n/a.

Tamura A, Yamada N, Yaguchi Y, Machida Y, Mori I, Osanai M. Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum. PLOS ONE. 2014 Jan 15;9(1):e85351.

Mazzoni A, Broccard FD, Garcia-Perez E, Bonifazi P, Ruaro ME, Torre V. On the dynamics of the spontaneous activity in neuronal networks. PLoS ONE. 2007 May 9;2(5):e439.

Cossart R, Aronov D, Yuste R. Attractor dynamics of network UP states in the neocortex. Nature. 2003 May 15;423(6937):283-8.

Mao B-Q, Hamzei-Sichani F, Aronov D, Froemke RC, Yuste R. Dynamics of spontaneous activity in neocortical slices. Neuron. 2001 Dec;32(5):883-98.

Piet R, Jahr CE. Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J Neurosci. 2007 Apr 11;27(15):4027-35.

Rojas A, Wetherington J, Shaw R, Serrano G, Swanger S, Dingledine R. Activation of group I metabotropic glutamate receptors potentiates heteromeric kainate receptors. Mol Pharmacol. 2013 Jan;83(1):106-21.

Sengupta M, Thirumalai V. AMPA receptor mediated synaptic excitation drives state-dependent bursting in Purkinje neurons of zebrafish larvae. eLife. 2015 Sep 29;4:e09158.

Parga N, Abbott LF. Network model of spontaneous activity exhibiting synchronous transitions between up and down states. Front Neurosci. 2007 Oct 15;1(1):57-66.

Wadsworth GP, Bryan JG. Introduction to probability and random variables. McGraw-Hill; 1960. 312 p.

Charles AC, Merrill JE, Dirksen ER, Sanderson MJ. Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron. 1991 Jun;6(6):983-92.

Ito D, Tamate H, Nagayama M, Uchida T, Kudoh SN, Gohara K. Minimum neuron density for synchronized bursts in a rat cortical culture on multi-electrode arrays. Neuroscience. 2010 Nov 24;171(1):50-61.

Pozzi D, Ban J, Iseppon F, Torre V. An improved method for growing neurons: Comparison with standard protocols. J Neurosci Methods. 2017 Mar;280:1-10.

Ulloa Severino FP, Ban J, Song Q, Tang M, Bianconi G, Cheng G, et al. The role of dimensionality in neuronal network dynamics. Sci Rep. 2016 Jul 11;6:29640.

Gentet LJ, Avermann M, Matyas F, Staiger JF, Petersen CCH. Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron. 2010 Feb;65(3):422-35.

Fukushima K. A hierarchical neural network model for associative memory. Biol Cybern. 1984 Apr 1;50(2):105-13.

Rolls ET. Cerebral cortex: principles of operation. First edition. Oxford New York, NY: Oxford University Press; 2016. 958 p.

Beggs JM, Plenz D. Neuronal avalanches in neocortical circuits. J Neurosci. 2003 Dec 3;23(35):11167-77.

Klaus A, Yu S, Plenz D. Statistical analyses support power law distributions found in neuronal avalanches. PLoS ONE. 2011 May 26;6(5):e19779.

Bak P, Tang C, Wiesenfeld K. Self-organized criticality: an explanation of the 1/f noise. Phys Rev Lett. 1987 Jul 27;59(4):381-4.

Hu W, Bean BP. Differential control of axonal and somatic resting potential by voltage-dependent conductances in cortical layer 5 pyramidal neurons. Neuron. 2018 Mar 21;97(6):1315-1326.e3.

Schröter M, Paulsen O, Bullmore ET. Micro-connectomics: probing the organization of neuronal networks at the cellular scale. Nat Rev Neurosci. 2017;18(3):131-46.

Marsili M, Valleriani A. Self Organization of Interacting Polya Urns. Eur Phys J B. 1998 Jul;3(4):417–20.

Morgan RJ, Soltesz I. Nonrandom connectivity of the epileptic dentate gyrus predicts a major role for neuronal hubs in seizures. Proc Natl Acad Sci USA. 2008 Apr 22;105(16):6179-84.

How to Cite
Pozzi, D., Meneghetti, N., Roy, A., Pastore, B., Mazzoni, A., Marsili, M., & Torre, V. (2020). The role of network architecture in the onset of spontaneous activity. STEMedicine, 1(1), e1.
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