Skip to main content
SpringerLink
Log in

A neglected GABAergic astrocyte: Calcium dynamics and involvement in seizure activity

  • Article
  • Published:
Science China Technological Sciences Aims and scope Submit manuscript

Abstract

Gamma-aminobutyric acid (GABA) contributes substantially to neurocognitive function as an important inhibitory neurotransmitter in the human cerebral cortex. However, the pathophysiology of disorders such as epilepsy are not well understood, since GABA agonists are not quite effective in treating epilepsy. Knowledge of the mechanism of action of GABA would contribute to review previously proposed anti-epileptic processes by GABA agonists. In this study based on recent experiments on GABAergic astrocytes, we developed a modified GABAergic astrocyte model, and successfully simulated a long-lasting Ca2+ oscillation in astrocytes after 0.5-s stimulation of GABAergic transmission. We then incorporated this GABAergic astrocyte model into a classical Ullah-Schiff seizure model and surprisingly found that this GABAergic astrocyte model functions to hinder the anti-epileptic action of GABA agonists, thereby explaining their low efficiency in previous experiments. These results also update our knowledge of the mechanism of action of GABA and the effects of astrocytes on physiological and pathological functions of the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Purves D, Augustine G, Fitzpatrick D, et al. Neuroscience. 4th Ed. Sunderland, MA: Sinauer Associates, Incorporated, 2008

    Google Scholar 

  2. Chavas J, Marty A. Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network. J Neurosci, 2003, 23: 2019–2031

    Google Scholar 

  3. Roberts E, Fnnkel S. Gamma-aminobutyric acid in brain: Its formation from glutrrmic acid. J Biol Chem, 1950, 187: 55–63

    Google Scholar 

  4. Awapara J, Landua A J, Fuerst R, et al. Free γ-aminobutyric acid in brain. J Biol Chem, 1950, 187: 35–39

    Google Scholar 

  5. Florey E, McLennan H. The release of an inhibitory substance from mammalian brain, and its effect on peripheral synaptic transmission. J Physiol, 1955, 129: 384–392

    Article  Google Scholar 

  6. Elliottand K A C, Gelder N M. Occlusion and metabolism of γ-aminobutyric acid by brain tissue. J Neurochem, 1958, 3: 28–40

    Article  Google Scholar 

  7. Dichter M A. Physiological identification of GABA as the inhibitory transmitter for mammalian cortical neurons in cell culture. Brain Res, 1980, 190: 111–121

    Article  Google Scholar 

  8. Bernardi G, Marciani M G, Stanzione P, et al. Evidence in favour of GABA as an inhibitory transmitter in the rat striatum. Adv Biochem Psychopharmacol, 1981, 30: 69–77

    Google Scholar 

  9. Represa A, Ben-Ari Y. Trophic actions of GABA on neuronal development. Trends Neurosci, 2005, 28: 278–283

    Article  Google Scholar 

  10. Zarrindast M R, Noorbakhshnia M, Motamedi F, et al. Effect of the GABAergic system on memory formation and state-dependent learning induced by morphine in rats. Pharmacology, 2006, 76: 93–100

    Article  Google Scholar 

  11. Tellez R, Gómez-Viquez L, Liy-Salmeron G, et al. GABA, glutamate, dopamine and serotonin transporters expression on forgetting. Neurobiol Learning Memory, 2012, 98: 66–77

    Article  Google Scholar 

  12. Gale K. GABA and epilepsy: Basic concepts from preclinical research. Epilepsia, 1992, 33 Suppl 5: S3–S12

    Google Scholar 

  13. Bradford H F. Glutamate, GABA and epilepsy. Prog Neurobiol, 1995, 47: 477–511

    Article  Google Scholar 

  14. Brooks-Kayal A R, Shumate M D, Jin H, et al. Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy. Nat Med, 1998, 4: 1166–1172

    Article  Google Scholar 

  15. Kandel E R, Schwartz J H, Jessell T M, et al. Principles of Neural Science. New York: McGraw-Hill, 2000

    Google Scholar 

  16. Guo D, Li C. Stochastic resonance in Hodgkin-Huxley neuron induced by unreliable synaptic transmission. J Theor Biol, 2012, 308: 105–114

    Article  MathSciNet  Google Scholar 

  17. Uzuntarla M. Inverse stochastic resonance induced by synaptic background activity with unreliable synapses. Phys Lett A, 2013, 377: 2585–2589

    Article  MathSciNet  MATH  Google Scholar 

  18. Deng B, Wang J, Wei X. Effect of chemical synapse on vibrational resonance in coupled neurons. Chaos, 2009, 19: 013117

    Article  Google Scholar 

  19. Perc M. Optimal spatial synchronization on scale-free networks via noisy chemical synapses. Biophysical Chem, 2009, 141: 175–179

    Article  Google Scholar 

  20. Burić N, Todorović K, Vasović N. Synchronization of bursting neurons with delayed chemical synapses. Phys Rev E, 2008, 78: 036211

    Article  Google Scholar 

  21. Zhao Z, Gu H. The influence of single neuron dynamics and network topology on time delay-induced multiple synchronous behaviors in inhibitory coupled network. Chaos Solitons Fractals, 2015, 80: 96–108

    Article  MathSciNet  MATH  Google Scholar 

  22. Wang Q Y, Lu Q S, Zheng Y H. Conduction delay-aided synchronization in two coupled chay neurons with inhibitory synapse. Acta Bioph Sin, 2005, 21: 449–456

    Google Scholar 

  23. Wang X J, Buzsák G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model, J Neurosci, 1996, 16: 6402–6413

    Google Scholar 

  24. Volk D W, Gonzalez-Burgos G, Lewis D A. l-Proline, GABA synthesis and gamma oscillations in schizophrenia. Trends Neurosci, 2016, 39: 797–798

    Article  Google Scholar 

  25. Fábera P, Mareš P. Effect of GABA(B) receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges. Physiol Res, 2014, 63: 529–534

    Google Scholar 

  26. Pedley T A, Horton R W, Meldrum B S. Electroencephalographic and behavioral effects of a GABA agonist (muscimol) on photosensitive epilepsy in the baboon, papio papio. Epilepsia, 1979, 20: 409–416

    Article  Google Scholar 

  27. Nakata M, Mukawa J, Fromm G H. Why are most GABA agonists not effective antiepileptic drugs? Jpn J Psychiatry Neurol, 1991, 45: 391–394

    Google Scholar 

  28. Kocsis J D, Mattson R H. GABA levels in the brain: A target for new antiepileptic drugs. Neuroscientist, 1996, 2: 326–334

    Article  Google Scholar 

  29. Mares P, Lindovský J, Slamberová R, et al. Effects of a GABA-B receptor agonist baclofen on cortical epileptic afterdischarges in rats. Epileptic Disord, 2007, 9 Suppl 1: S44–S51

    Google Scholar 

  30. Mares P, Tabashidze N. Contradictory effects of GABA-B receptor agonists on cortical epileptic afterdischarges in immature rats. Brain Res Bull, 2008, 75: 173–178

    Article  Google Scholar 

  31. Fiacco T A, Agulhon C, McCarthy K D. Sorting out astrocyte physiology from pharmacology. Annu Rev Pharmacol Toxicol, 2009, 49: 151–174

    Article  Google Scholar 

  32. Charles A C, Merrill J E, Dirksen E R, et al. Intercellular signaling in glial cells: Calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron, 1991, 6: 983–992

    Article  Google Scholar 

  33. Pasti L, Volterra A, Pozzan T, et al. Intracellular calcium oscillations in astrocytes: A highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci, 1997, 17: 7817–7830

    Google Scholar 

  34. Parpura V, Haydon P G. Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc Natl Acad Sci USA, 2000, 97: 8629–8634

    Article  Google Scholar 

  35. Parri H R, Gould T M, Crunelli V. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci, 2001, 4: 803–812

    Article  Google Scholar 

  36. Araque A, Parpura V, Sanzgiri R P, et al. Tripartite synapses: Glia, the unacknowledged partner. Trends Neurosci, 1999, 22: 208–215

    Article  Google Scholar 

  37. Araque A, Carmignoto G, Haydon P G. Dynamic signaling between astrocytes and neurons. Annu Rev Physiol, 2001, 63: 795–813

    Article  Google Scholar 

  38. Perea G, Navarrete M, Araque A. Tripartite synapses: Astrocytes process and control synaptic information. Trends Neurosci, 2009, 32: 421–431

    Article  Google Scholar 

  39. Volman V, Ben-Jacob E, Levine H. The astrocyte as a gatekeeper of synaptic information transfer. Neural Comput, 2007, 19: 303–326

    Article  MathSciNet  MATH  Google Scholar 

  40. Tang J, Luo J M, Ma J. Information transmission in a neuron-astrocyte coupled model. PLoS ONE, 2013, 8: e80324

    Google Scholar 

  41. Li J J, Du M M, Wang R, et al. Astrocytic gliotransmitter: Diffusion dynamics and induction of information processing on tripartite synapses. Int J Bifurcation Chaos, 2016, 26: 1650138

    Article  MathSciNet  MATH  Google Scholar 

  42. Vélez-Fort M, Audinat E, Angulo M C. Central role of GABA in neuron- glia interactions. Neuroscientist, 2012, 18: 237–250

    Article  Google Scholar 

  43. Losi G, Mariotti L, Carmignoto G. GABAergic interneuron to astrocyte signalling: A neglected form of cell communication in the brain. Philos Trans R Soc B-Biol Sci, 2014, 369: 20130609

    Article  Google Scholar 

  44. Shigetomi E, Patel S, Khakh B S. Probing the complexities of astrocyte calcium signaling. Trends Cell Biol, 2016, 26: 300–312

    Article  Google Scholar 

  45. Bazargani N, Attwell D. Astrocyte calcium signaling: The third wave. Nat Neurosci, 2016, 19: 182–189

    Article  Google Scholar 

  46. Mariotti L, Losi G, Sessolo M, et al. The inhibitory neurotransmitter GABA evokes long-lasting Ca2+ oscillations in cortical astrocytes. Glia, 2016, 64: 363–373

    Article  Google Scholar 

  47. Pinsky P F, Rinzel J. Intrinsic and network rhythmogenesis in a reduced traub model for CA3 neurons. J Comput Neurosci, 1994, 1: 39–60

    Article  Google Scholar 

  48. Amiri M, Bahrami F, Janahmadi M. Functional contributions of astrocytes in synchronization of a neuronal network model. J Theor Biol, 2012, 292: 60–70

    Article  MathSciNet  MATH  Google Scholar 

  49. Ullah G, Schiff S J. Assimilating seizure dynamics. PLoS Comput Biol, 2010, 6: e1000776

    Google Scholar 

  50. Nadkarni S, Jung P. Modeling synaptic transmission of the tripartite synapse. Phys Biol, 2007, 4: 1–9

    Article  Google Scholar 

  51. Ullah G, Jung P, Cornell-Bell A H. Anti-phase calcium oscillations in astrocytes via inositol (1,4,5)-trisphosphate regeneration. Cell Calcium, 2006, 39: 197–208

    Article  Google Scholar 

  52. Li J, Tang J, Ma J, et al. Dynamic transition of neuronal firing induced by abnormal astrocytic glutamate oscillation. Sci Rep, 2016, 6: 32343

    Article  Google Scholar 

  53. Sahlender D A, Savtchouk I, Volterra A. What do we know about gliotransmitter release from astrocytes? Philos Trans R Soc B-Biol Sci, 2014, 369: 20130592

    Article  Google Scholar 

  54. Guo D, Wu S, Chen M, et al. Regulation of irregular neuronal firing by autaptic transmission. Sci Rep, 2016, 6: 26096

    Article  Google Scholar 

  55. Yilmaz E, Baysal V, Perc M, et al. Enhancement of pacemaker induced stochastic resonance by an autapse in a scale-free neuronal network. Sci China Tech Sci, 2016, 59: 364–370

    Article  Google Scholar 

  56. Manning T J, Sontheimer H. Spontaneous intracellular calcium oscillations in cortical astrocytes from a patient with intractable childhood epilepsy (Rasmussen’s Encephalitis). Glia, 1997, 21: 332–337

    Article  Google Scholar 

  57. Balázsi G, Cornell-Bell A H, Moss F. Increased phase synchronization of spontaneous calcium oscillations in epileptic human versus normal rat astrocyte cultures. Chaos, 2003, 13: 515–518

    Article  Google Scholar 

  58. Kanemaru K, Okubo Y, Hirose K, et al. Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes. J Neurosci, 2007, 27: 8957–8966

    Article  Google Scholar 

  59. Bikson M, Hahn P J, Fox J E, et al. Depolarization block of neurons during maintenance of electrographic seizures. J Neurophysiol, 2003, 90: 2402–2408

    Article  Google Scholar 

  60. Cressman Jr J R, Ullah G, Ziburkus J, et al. The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. Single neuron dynamics. J Comput Neurosci, 2009, 26: 159–170

    Article  MathSciNet  Google Scholar 

  61. Du M, Li J, Wang R, et al. The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus. Cogn Neurodyn, 2016, 10: 405–414

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi’an Jiaotong University, Xi’an, 710049, China

    JiaJia Li, Yong Xie, MengMeng Du, Rong Wang & Ying Wu

  2. Center for Computational Systems Biology, Fudan University, Shanghai, 200433, China

    YuGuo Yu

  3. Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu, 610054, China

    Ying Wu

Authors
  1. JiaJia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. YuGuo Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. MengMeng Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying Wu.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Xie, Y., Yu, Y. et al. A neglected GABAergic astrocyte: Calcium dynamics and involvement in seizure activity. Sci. China Technol. Sci. 60, 1003–1010 (2017). https://doi.org/10.1007/s11431-016-9056-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11431-016-9056-2

Keywords

Search

Navigation