Abstract
Neural synchronization is considered as an important mechanism for information processing. In addition, based on recent neurophysiologic findings, it is believed that astrocytes regulate the synaptic transmission of neuronal networks. Therefore, the present study focused on determining the functional contribution of astrocytes in neuronal synchrony using both computer simulations and extracellular field potential recordings. For computer simulations, as a first step, a minimal network model is constructed by connecting two Morris-Lecar neuronal models. In this minimal model, astrocyte-neuron interactions are considered in a functional-based procedure. Next, the minimal network is extended and a biologically plausible neuronal population model is developed which considers functional outcome of astrocyte-neuron interactions too. The employed structure is based on the physiological and anatomical network properties of the hippocampal CA1 area. Utilizing these two different levels of modeling, it is demonstrated that astrocytes are able to change the threshold value of transition from synchronous to asynchronous behavior among neurons. In this way, variations in the interaction between astrocytes and neurons lead to the emergence of synchronous/asynchronous patterns in neural responses. Furthermore, population spikes are recorded from CA1 pyramidal neurons in rat hippocampal slices to validate the modeling results. It demonstrates that astrocytes play a primary role in neuronal firing synchronicity and synaptic coordination. These results may offer a new insight into understanding the mechanism by which astrocytes contribute to stabilizing neural activities.
Similar content being viewed by others
References
Ackert, J. M., Wu, S. H., Lee, J. C., Abrams, J., Hu, E. H., Perlman, I., & Bloomfield, S. A. (2006). Light-induced changes in spike synchronization between coupled ON direction selective ganglion cells in the mammalian retina. Journal of Neuroscience, 26, 4206–4215.
Aguado, F., Espinosa-Parrilla, J. F., Carmona, M. A., & Soriano, E. (2002). Neuronal activity regulates correlated network properties of spontaneous calcium transients in astrocytes in situ. Journal of Neuroscience, 22, 9430–9444.
Agulhon, C., Fiacco, T. A., & McCarthy, K. D. (2010). Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science, 327(5970), 1250–1254.
Amiri, M., Davoodi, E., Bahrami, F., & Raza, M. (2011a). Bifurcation analysis of the Poincaré map function of intracranial EEG signals in temporal lobe epilepsy patients. Mathematics and Computers in Simulation, 81, 2471–2491.
Amiri, M., Bahrami, F., & Janahmadi, M. (2011b). Functional modeling of astrocytes in epilepsy: a feedback system perspective. Neural Computing and Applications, 20(8), 1131–1139.
Amiri, M., Montaseri, G., & Bahrami, F. (2011c). On the role of astrocytes in synchronization of two coupled neurons: a mathematical perspective. Biological Cybernetics, 105, 153–166.
Amiri, M., Bahrami, F., & Janahmadi, M. (2012a). Functional contributions of astrocytes in synchronization of a neuronal network model. Journal of Theoretical Biology, 292, 60–70.
Amiri, M., Bahrami, F., & Janahmadi, M. (2012b). On the role of astrocytes in epilepsy: a functional modeling approach. Neuroscience Research, 7, 172–180.
Amiri, M., Bahrami, F., & Janahmadi, M. (2012c). Modified thalamocortical model: a step towards more understanding of the functional contribution of astrocytes to epilepsy. Journal of Computational Neuroscience, 33, 285–299.
Angulo, M. C., Kozlov, A. S., Charpak, S., & Audinat, E. (2004). Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. Journal of Neuroscience, 24, 6920–6927.
Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1998a). Glutamatedependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. European Journal of Neuroscience, 10, 2129–2142.
Araque, A., Sanzgiri, R. P., Parpura, V., & Haydon, P. G. (1998b). Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. Journal of Neuroscience, 18, 6822–6829.
Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1999). Tripartite synapses: glia, the unacknowledged partner. Trends in Neurosciences, 22, 208–215.
Benda, J., Longtin, A., & Maler, L. (2006). A synchronization-desynchronization code for natural communication signals. Neuron, 52, 347–358.
Bushong, E. A., Martone, M. E., Jones, Y. Z., & Ellisman, M. H. (2002). Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. Journal of Neuroscience, 22, 183–192.
Chakravarthy, N., Sabesan, S., Iasemidis, L. D., & Tsakalis, K. (2007). Modeling and controlling synchronization in a neuron level population model. International Journal of Neural Systems, 17, 123–138.
Chakravarthy, N., Tsakalis, K., Sabesan, S., & Iasemidis, L. D. (2009). Homeostasis of brain dynamics in epilepsy: a feedback control systems perspective of seizures. Annals of Biomedical Engineering, 37, 565–585.
Cressman, J. R., Jr., Ullah, G., Ziburkus, J., Schiff, S. J., & Barreto, E. (2009). The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. Single neuron dynamics. Journal of Computational Neuroscience, 26, 159–170.
Demont-Guignard, S., Benquet, P., Gerber, U., & Wendling, F. (2009). Analysis of intracerebral EEG recordings of epileptic spikes: insights from a neural network model. IEEE Transactions on Biomedical Engineering, 56, 2782–2795.
Di Castro, M. A., Chuquet, J., Liaudet, N., Bhaukaurally, K., Santello, M., Bouvier, D., Tiret, P., & Volterra, A. (2011). Local Ca2+ detection and modulation of synaptic release by astrocytes. Nature Neuroscience, 14(10), 1276–1284.
Fellin, T. (2009). Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity. Journal of Neurochemistry, 108, 533–544.
Fellin, T., Pascual, O., & Haydon, P. G. (2006). Astrocytes coordinate synaptic networks: balanced excitation and inhibition. The Journal of Physiology, 21, 208–215.
Fiacco, T. A., & McCarthy, K. D. (2004). Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons. Journal of Neuroscience, 24, 722–732.
Fiacco, T. A., Agulhon, C., Taves, S. R., Petravicz, J., Casper, K. B., Dong, X., Chen, J., & McCarthy, K. D. (2007). Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron, 24, 611–625.
Garwood, C. J., Pooler, A. M., Atherton, J., Hanger, D. P., & Noble, W. (2011). Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death & Disease, 2, e167.
Giugliano, M. (2009). Calcium waves in astrocyte networks: theory and experiments. Frontiers in Computational Neuroscience, 3, 160–161.
Gross, J., Schmitz, F., Schnitzler, I., Kessler, K., Shapiro, K., Hommel, B., & Schnitzler, A. (2004). Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans. Proceedings of the National Academy of Sciences of the United States of America, 101(35), 13050–13055.
Halassa, M. M., Fellin, T., Takano, H., Dong, J. H., & Haydon, P. G. (2007). Synaptic islands defined by the territory of a single astrocyte. Journal of Neuroscience, 27, 6473–6477.
Halassa, M. M., Fellin, T., & Haydon, P. G. (2009a). Tripartite synapses: roles for astrocytic purines in the control of synaptic physiology and behavior. Neuropharmacology, 57, 343–346.
Halassa, M. M., Florian, C., Fellin, T., Munoz, J. R., Lee, S. Y., Abel, T., Haydon, P. G., & Frank, M. G. (2009b). Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron, 61, 213–219.
Hamilton, N. B., & Attwell, D. (2010). Do astrocytes really exocytose neurotransmitters? Nature Reviews Neuroscience, 11(4), 227–238.
Hauptmann, C., Popovych, O., & Tass, P. A. (2005). Effectively desynchronizing deep brain stimulation based on coordinated delayed feedback stimulation via several sites: a computational study. Biological Cybernetics, 93, 463–470.
Haydon, P. G., & Araque, A. (2002). Astrocytes as modulators of synaptic transmission. In: The tripartite synapse: Glia in synaptic transmission (pp. 185–198). New York: Oxford UP.
Haydon, P. G., & Carmignoto, G. (2006). Astrocyte control of synaptic transmission and neurovascular coupling. Physiological Reviews, 86(3), 1009–1031.
Jedlicka, P., Deller, T., & Schwarzacher, S. W. (2010). Computational modeling of GABAA receptor-mediated paired-pulse inhibition in the dentate gyrus. Journal of Computational Neuroscience, 29, 509–519.
Jourdain, P., Bergersen, L. H., Bhaukaurally, K., Bezzi, P., Santello, M., Domercq, M., Matute, C., Tonello, F., Gundersen, V., & Volterra, A. (2007). Glutamate exocytosis from astrocytes controls synaptic strength. Nature Neuroscience, 10, 331–339.
Kandel, E. R., Schwartz, J. H., & Jessell, T. M. (2000). Principles of neural science (4th ed.). New York: McGraw-Hill.
Koizumi, S. (2010). Synchronization of Ca2+ oscillations: involvement of ATP release in astrocytes. FEBS Journal, 277, 286–292.
Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T., & Bacskai, B. J. (2009). Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science, 323, 1211–1215.
Kuga, N., Sasaki, T., Takahara, Y., Matsuki, N., & Ikegaya, Y. (2011). Large-scale calcium waves traveling through astrocytic networks in vivo. The Journal of Neuroscience, 31(7), 2607–2614.
Li, Y., & Rinzel, J. (1994). Equations for inositol-triphosphate receptor-mediated calcium oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism. Journal of Theoretical Biology, 166, 461–473.
Liu, X. D., Wang, J. J, Sun, L., Chen, L. W, Rao, Z. R, Duan, L., Cao, R., Wang, M. Q. (2009). Involvement of medullary dorsal horn glial cell activation in mediation of masseter mechanical allodynia induced by experimental tooth movement. Archives of Oral Biology.
Luo, M., Wu, Y., & Peng, J. (2009). Washout filter aided mean field feedback desynchronization in an ensemble of globally coupled neural oscillators. Biological Cybernetics, 101, 241–246.
Montaseri, G., Yazdanpanah, M. J., Amiri, M. (2011). Astrocyte-inspired controller design for desynchronization of two coupled limit-cycle oscillators, third world congress on nature and biologically inspired computing (pp. 195–200).
Morris, C., & Lecar, H. (1981). Voltage oscillations in the barnacle giant muscle fiber. Biophysical Journal, 35, 193–213.
Nadkarni, S., & Jung, P. (2004). Dressed neurons: modeling neural-glial interactions. Physical Biology, 1, 35–41.
Nadkarni, S., & Jung, P. (2007). Modeling synaptic transmission of the tripartite synapse. Physical Biology, 4, 1–9.
Newman, E. A. (2003). New roles for astrocytes: regulation of synaptic transmission. Trends in Neurosciences, 26, 536–542.
Occhipinti, R., Somersalo, E., & Calvetti, D. (2009). Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study. Journal of Neurophysiology, 101, 2528–2538.
Omrani, M. R., Ghadami, N., Fathi, M., Tahmasian, Y., Fathollahi, & Touhidi, A. (2007). Naloxone improves impairment of spatial performance induced by pentylentetrazol kindling in rats. Neuroscience, 145, 824–831.
Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J. Y., Takano, H., Moss, S. J., McCarthy, K., & Haydon, P. G. (2005). Astrocytic purinergic signaling coordinates synaptic networks. Science, 310, 113–116.
Perea, G., & Araque, A. (2005). Properties of synaptically evoked astrocyte calcium signal reveal synaptic information processing by astrocytes. Journal of Neuroscience, 25, 2192–2203.
Perea, G., & Araque, A. (2007). Astrocytes potentiate transmitter release at single hippocampal synapses. Science, 317(5841), 1083–1108.
Perea, G., Navarrete, M., & Araque, A. (2009). Tripartite synapses: astrocytes process and control synaptic information. Trends in Neurosciences, 32, 421–431.
Popovych, O. V., Hauptmann, C., & Tass, P. A. (2006). Control of neuronal synchrony by nonlinear delayed feedback. Biological Cybernetics, 95, 69–85.
Porto-Pazos, A. B., Veiguela, N., Mesejo, P., Navarrete, M., Alvarellos, A., Ibanez, O., Pazos, A., & Araque, A. (2011). Artificial astrocytes improve neural network performance. PLoS One, 6(4), e19109. doi:10.1371/journal.pone.0019109.
Postnov, D. E., Ryazanov, L. S., & Sosnovtseva, O. V. (2007). Functional modeling of neural-glial interaction. Bio Systems, 89, 84–91.
Postnov, D. E., Koreshkov, R. N., Brazhe, N. A., Brazhe, A. R., & Sosnovtseva, O. V. (2009). Dynamical patterns of calcium signaling in a functional model of neuron-astrocyte networks. Journal of Biological Physics, 35, 425–445.
Rinzel, J., & Ermentrout, G. B. (1989). Analysis of neural excitability and oscillations. In C. H. Koch & I. Segev (Eds.), Methods in neuronal modelling from synapses to networks (pp. 135–169). Cambridge: MIT Press.
Rusakov, D. A., Zheng, K., & Henneberger, C. (2011). Astrocytes as regulators of synaptic function: a quest for the Ca2+ master key. The Neuroscientist, 17, 513–523.
Sasaki, T., Kuga, N., Namiki, S., Matsuki, N., Ikegaya, Y. (2011). Locally synchronized astrocytes. Cereb Cortex. Advance online publication. Retrieved January 18, 2011. doi:10.1093/cercor/bhq256.
Schnitzler, A., & Gross, J. (2005). Normal and pathologicaloscillatory communication in the brain. Nature Reviews Neuroscience, 6, 285–296.
Serrano, A., Haddjeri, N., Lacaille, J. C., & Robitaille, R. (2006). GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression. Journal of Neuroscience, 26, 5370–5382.
Sotero, R. C., & Martínez-Cancino, R. (2010). Dynamical mean field model of a neural-glial mass. Neural Computation, 22, 969–997.
Takata, N., & Hirase, H. (2008). Cortical layer 1 and layer 2/3 astrocytes exhibit distinct calcium dynamics in vivo. PLoS One, 3, e2525.
Tass, P. A., & Hauptmann, C. (2007). Therapeutic modulation of synaptic connectivity with desynchronizing brain stimulation. International Journal of Psychophysiology, 64, 53–61.
Terman, D., Rubin, J. E., Yew, A. C., & Wilson, C. J. (2002). Activity patterns in a model for the subthalamopallidal network of the basal ganglia. The Journal of Neuroscience, 22, 2963–2976.
Tian, G. F., Azmi, H., Takano, T., Xu, Q., Peng, W., Lin, J., Oberheim, N., Lou, N., Wang, X., Zielke, H. R., et al. (2005). An astrocytic basis of epilepsy. Nature Medicine, 11, 973–981.
Ullah, G., Jung, P., & Cornell-Bell, A. H. (2006). Anti-phase calcium oscillations in astrocytes via inositol (1,4,5)-trisphosphate regeneration. Cell Calcium, 39, 197–208.
Ullah, G., Cressman, J. R., Jr., Barreto, E., & Schiff, S. J. (2009). The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: II. Network and glial dynamics. Journal of Computational Neuroscience, 26, 171–183.
Volman, V., Ben-Jacob, E., & Levine, H. (2007). The astrocyte as a gatekeeper of synaptic information transfer. Neural Computation, 19, 303–326.
Ward, L. M. (2003). Synchronous neural oscillations and cognitive processes. Trends in Cognitive Sciences, 7, 553–559.
Wenker, I. (2010). An active role for astrocytes in synaptic plasticity? Journal of Neurophysiology, 104, 1216–1218. doi:10.1152/jn.00429.
Wetherington, J., Serrano, G., & Dingledine, R. (2008). Astrocytes in the epileptic brain. Neuron, 58, 168–178.
Zhang, J., Wang, H., Ye, C., Ge, W., Chen, Y., Jiang, Z., Wu, C., Poo, M., & Duan, S. (2003). ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron, 40, 971–982.
Author information
Authors and Affiliations
Corresponding author
Additional information
Action Editor: Catherine E. Carr
Rights and permissions
About this article
Cite this article
Amiri, M., Hosseinmardi, N., Bahrami, F. et al. Astrocyte- neuron interaction as a mechanism responsible for generation of neural synchrony: a study based on modeling and experiments. J Comput Neurosci 34, 489–504 (2013). https://doi.org/10.1007/s10827-012-0432-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10827-012-0432-6