Research article Special Issues

The important role of astrocytes in activity pattern transition of the subthalamopallidal network related to Parkinson's disease

  • Received: 30 December 2023 Revised: 29 May 2024 Accepted: 12 June 2024 Published: 26 June 2024
  • This paper integrates astrocytes into the subthalamopallodal network model associated with Parkinson's disease (PD) to simulate the firing activity of this circuit. Under different network connectivity modes, we primarily investigate the role of astrocytes in the discharge rhythm of the subthalamic nucleus (STN) and the external segment of the globus pallidus (GPe). First, with varying synaptic coupling, the STN-GPe model generates five typical waveforms corresponding to the severity of PD symptoms in a sparsely coupled network in turn. Subsequently, astrocytes are included in the STN-GPe circuit. When they have an inhibitory effect on the STN and an excitatory effect on the GPe, the pathological discharge pattern of the network can be destroyed or even eliminated under appropriate conditions. At the same time, the high degree of synchrony between neurons and the power of the beta band weakens. In addition, we find that the astrocytic effect on the GPe plays a dominant role in the regulatory process. Finally, the tightly coupled network can also generate five different, highly correlated sustained discharge waveforms, including in-phase and anti-phase cluster synchronization. The effective regulation of the pathological state of PD, which involves improvements in the discharge patterns, synchronization, and beta oscillations, is achieved when astrocytes inhibit the STN and excite the GPe. It is worth noting that the regulatory influence of astrocytes on PD is shown to be robust, and independent of the network connectivity, to some extent. This work contributes to understanding the role of astrocytes in PD, providing insights for the treatment and regulation of PD.

    Citation: Yuzhi Zhao, Honghui Zhang, Zilu Cao. The important role of astrocytes in activity pattern transition of the subthalamopallidal network related to Parkinson's disease[J]. Electronic Research Archive, 2024, 32(6): 4108-4128. doi: 10.3934/era.2024185

    Related Papers:

  • This paper integrates astrocytes into the subthalamopallodal network model associated with Parkinson's disease (PD) to simulate the firing activity of this circuit. Under different network connectivity modes, we primarily investigate the role of astrocytes in the discharge rhythm of the subthalamic nucleus (STN) and the external segment of the globus pallidus (GPe). First, with varying synaptic coupling, the STN-GPe model generates five typical waveforms corresponding to the severity of PD symptoms in a sparsely coupled network in turn. Subsequently, astrocytes are included in the STN-GPe circuit. When they have an inhibitory effect on the STN and an excitatory effect on the GPe, the pathological discharge pattern of the network can be destroyed or even eliminated under appropriate conditions. At the same time, the high degree of synchrony between neurons and the power of the beta band weakens. In addition, we find that the astrocytic effect on the GPe plays a dominant role in the regulatory process. Finally, the tightly coupled network can also generate five different, highly correlated sustained discharge waveforms, including in-phase and anti-phase cluster synchronization. The effective regulation of the pathological state of PD, which involves improvements in the discharge patterns, synchronization, and beta oscillations, is achieved when astrocytes inhibit the STN and excite the GPe. It is worth noting that the regulatory influence of astrocytes on PD is shown to be robust, and independent of the network connectivity, to some extent. This work contributes to understanding the role of astrocytes in PD, providing insights for the treatment and regulation of PD.


    加载中


    [1] S. Mullin, A. H. V. Schapira, Pathogenic mechanisms of neurodegeneration in Parkinson disease, Neurol. Clin., 33 (2015), 1–17. https://doi.org/10.1016/j.ncl.2014.09.010 doi: 10.1016/j.ncl.2014.09.010
    [2] A. Galvan, A. Devergnas, T. Wichmann, Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state, Front. Neuroanat., 9 (2015), 5. https://doi.org/10.3389/fnana.2015.00005 doi: 10.3389/fnana.2015.00005
    [3] P. Silberstein, A. KuÈhn, A. Kupsch, T. Trottenberg, J. Krauss, J. WoÈhrle, et al., Patterning of globus pallidus local field potentials differs between Parkinson's disease and dystonia, Brain, 126 (2003), 2597–2608. https://doi.org/10.1093/brain/awg267 doi: 10.1093/brain/awg267
    [4] S. Kim, E. Pajarillo, I. Nyarko-Danquah, M. Aschner, E. Lee, Role of astrocytes in Parkinson's disease associated with genetic mutations and neurotoxicants, Cells, 12 (2023), 622. https://doi.org/10.3390/cells12040622 doi: 10.3390/cells12040622
    [5] L. Iovino, M. E. Tremblay, L. Civiero, Glutamate-induced excitotoxicity in Parkinson's disease: the role of glial cells, J. Pharmacol. Sci., 144 (2020), 151–164. https://doi.org/10.1016/j.jphs.2020.07.011 doi: 10.1016/j.jphs.2020.07.011
    [6] H. Kwon, S. Koh, Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes, Transl. Neurodegener., 9 (2020), 42. https://doi.org/10.1186/s40035-020-00221-2 doi: 10.1186/s40035-020-00221-2
    [7] H. D. E. Booth, W. D. Hirst, R. Wade-Martins, The role of astrocyte dysfunction in Parkinson's disease pathogenesis, Trends Neurosci., 40 (2017), 358–370. https://doi.org/10.1016/j.tins.2017.04.001 doi: 10.1016/j.tins.2017.04.001
    [8] W. Chung, N. J. Allen, C. Eroglu, Astrocytes control synapse formation, function, and elimination, Cold Spring Harbor Perspect. Biol., 7 (2015), a020370. https://doi.org/10.1101/cshperspect.a020370 doi: 10.1101/cshperspect.a020370
    [9] I. Miyazaki, M. Asanuma, Neuron-astrocyte interactions in Parkinson's disease, Cells, 9 (2020), 2623. https://doi.org/10.3390/cells9122623 doi: 10.3390/cells9122623
    [10] N. Mallet, L. Delgado, M. Chazalon, C. Miguelez, J. Baufreton, Cellular and synaptic dysfunctions in Parkinson's disease: stepping out of the striatum, Cells, 8 (2019), 1005. https://doi.org/10.3390/cells8091005 doi: 10.3390/cells8091005
    [11] J. Giehrl-Schwab, F. Giesert, B. Rauser, C. L. Lao, S. Hembach, S. Lefort, et al., Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons, EMBO Mol. Med., 14 (2022), e14797. https://doi.org/10.15252/emmm.202114797 doi: 10.15252/emmm.202114797
    [12] K. Chen, H. Wang, I. Ilyas, A. Mahmood, L. Hou, Microglia and astrocytes dysfunction and key neuroinflammation-based biomarkers in Parkinson's disease, Brain Sci., 13 (2023), 634. https://doi.org/10.3390/brainsci13040634 doi: 10.3390/brainsci13040634
    [13] A. N. Brandebura, A. Paumier, T. S. Onur, N. J. Allen, Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders, Nat. Rev. Neurosci., 24 (2023), 23–39. https://doi.org/10.1038/s41583-022-00641-1 doi: 10.1038/s41583-022-00641-1
    [14] V. Volman, M. Bazhenov, T. J. Sejnowski, Computational models of neuron-astrocyte interaction in epilepsy, Front. Comput. Neurosci., 6 (2012), 58. https://doi.org/10.3389/fncom.2012.00058 doi: 10.3389/fncom.2012.00058
    [15] J. Tang, J. Zhang, J. Ma, G. Zhang, X. Yang, Astrocyte calcium wave induces seizure-like behavior in neuron network, Sci. China Technol. Sci., 60 (2017), 1011–1018. https://doi.org/10.1007/s11431-016-0293-9 doi: 10.1007/s11431-016-0293-9
    [16] D. A. Iacobas, S. O. Suadicani, D. C. Spray, E. Scemes, A stochastic two-dimensional model of intercellular Ca2+ wave spread in glia, Biophys. J., 90 (2006), 24–41. https://doi.org/10.1529/biophysj.105.064378 doi: 10.1529/biophysj.105.064378
    [17] A. N. Silchenko, P. A. Tass, Computational modeling of paroxysmal depolarization shifts in neurons induced by the glutamate release from astrocytes, Biol. Cybern., 98 (2008), 61–74. https://doi.org/10.1007/s00422-007-0196-7 doi: 10.1007/s00422-007-0196-7
    [18] D. Reato, M. Cammarota, L. C. Parra, G. Carmignoto, Computational model of neuron-astrocyte interactions during focal seizure generation, Front. Comput. Neurosci., 6 (2012), 81. https://doi.org/10.3389/fncom.2012.00081 doi: 10.3389/fncom.2012.00081
    [19] D. Terman, J. E. Rubin, A. C. Yew, C. J. Wilson, Activity patterns in a model for the subthalamopallidal network of the basal ganglia, J. Neurosci., 22 (2002), 2963–2976. https://doi.org/10.1523/JNEUROSCI.22-07-02963.2002 doi: 10.1523/JNEUROSCI.22-07-02963.2002
    [20] J. E. Rubin, D. Terman, High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model, J. Comput. Neurosci., 16 (2004), 211–235. https://doi.org/10.1023/B:JCNS.0000025686.47117.67 doi: 10.1023/B:JCNS.0000025686.47117.67
    [21] J. Best, C. Park, D. Terman, C. Wilson, Transitions between irregular and rhythmic firing patterns in excitatory-inhibitory neuronal networks, J. Comput. Neurosci., 23 (2007), 217–235. https://doi.org/10.1007/s10827-007-0029-7 doi: 10.1007/s10827-007-0029-7
    [22] V. Volman, E. Ben-Jacob, H. Levine, The astrocyte as a gatekeeper of synaptic information transfer, Neural Comput., 19 (2007), 303–326. https://doi.org/10.1162/neco.2007.19.2.303 doi: 10.1162/neco.2007.19.2.303
    [23] Z. Ouyang, Y. Yu, Z. Liu, P. Feng, Transition of spatiotemporal patterns in neuron–astrocyte networks, Chaos, Solitons Fractals, 169 (2023), 113222. https://doi.org/10.1016/j.chaos.2023.113222 doi: 10.1016/j.chaos.2023.113222
    [24] J. Zhao, D. Fan, Q. Wang, Q. Wang, Dynamical transitions of the coupled class Ⅰ (Ⅱ) neurons regulated by an astrocyte, Nonlinear Dyn., 103 (2021), 913–924. https://doi.org/10.1007/s11071-020-06122-3 doi: 10.1007/s11071-020-06122-3
    [25] M. Amiri, F. Bahrami, M. Janahmadi, Functional contributions of astrocytes in synchronization of a neuronal network model, J. Theor. Biol., 292 (2012), 60–70. https://doi.org/10.1016/j.jtbi.2011.09.013 doi: 10.1016/j.jtbi.2011.09.013
    [26] M. Amiri, N. Hosseinmardi, F. Bahrami, M. Janahmadi, Astrocyte-neuron interaction as a mechanism responsible for generation of neural synchrony: a study based on modeling and experiments, J. Comput. Neurosci., 34 (2013), 489–504. https://doi.org/10.1007/s10827-012-0432-6 doi: 10.1007/s10827-012-0432-6
    [27] J. J. Wade, L. J. McDaid, J. Harkin, V. Crunelli, J. A. S. Kelso, Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach, PLOS One, 6 (2011), e29445. https://doi.org/10.1371/journal.pone.0029445 doi: 10.1371/journal.pone.0029445
    [28] D. Fan, Q. Wang, Improving desynchronization of parkinsonian neuronal network via triplet-structure coordinated reset stimulation, J. Theor. Biol., 370 (2015), 157–170. https://doi.org/10.1016/j.jtbi.2015.01.040 doi: 10.1016/j.jtbi.2015.01.040
    [29] H. Zhang, Y. Yu, Z. Deng, Q. Wang, Activity pattern analysis of the subthalamopallidal network under ChannelRhodopsin-2 and Halorhodopsin photocurrent control, Chaos, Solitons Fractals, 138 (2020), 109963. https://doi.org/10.1016/j.chaos.2020.109963 doi: 10.1016/j.chaos.2020.109963
    [30] Z. Cao, L. Du, H. Zhang, Y. Zhao, Z. Shen, Z. Deng, Pattern transition and regulation in a subthalamopallidal network under electromagnetic effect, Chin. Phys. B, 31 (2022), 118701. https://doi.org/10.1088/1674-1056/ac80ae doi: 10.1088/1674-1056/ac80ae
    [31] H. Zhang, J. Su, Q. Wang, Y. Liu, L. Good, J. M. Pascual, Predicting seizure by modeling synaptic plasticity based on EEG signals-a case study of inherited epilepsy, Commun. Nonlinear Sci. Numer. Simul., 56 (2018), 330–343. https://doi.org/10.1016/j.cnsns.2017.08.020 doi: 10.1016/j.cnsns.2017.08.020
  • Reader Comments
  • © 2024 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(557) PDF downloads(37) Cited by(0)

Article outline

Figures and Tables

Figures(14)  /  Tables(1)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog