Skip to main content
SpringerLink
Log in

Inhibition of GABAergic Transmission as a Model of Hyperactivation of Purkinje Cells in the Rat Cerebellum

  • CELL BIOPHYSICS
  • Published:
Biophysics Aims and scope Submit manuscript

Abstract—Pathological changes in the cerebellum are often associated with dysfunction of Purkinje cells, which is manifested in excessive spike activity. In our experiments, the increase in the frequency of spike activity of Purkinje cells was caused by the suppression of inhibitory transmission by the GABA receptor antagonist gabazin (hydrobromide 6-imino-3-(4-methoxyphenyl)-1(6H)-pyrazinobutanic acid) contrary to the classical model of neurodegeneration, in which hyperactivation of neurons is caused by the long-term action of high concentrations of excitatory agonists (glutamate or N-methyl-D-aspartate). In adult and young animals, gabazine caused a significant increase in the frequency of Purkinje cell discharges after 25 and 45 min of action, respectively. Thus, this model worked more effectively in adult animals than in young ones, which is due to the ontogenetic features of the formation of the cerebellar cortex. Moreover, the use of NS 309 (6,7-dichloro-1H-indole-2,3-diketone-3-oxime), a modulator of Ca2+-activated K+ channels of small conductance, in this model made it possible to compensate for the increase in the frequency of simple spikes induced by the gabazine in the discharge of Purkinje cells to the level of the control values in young and adult rats.

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

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. M. Ito, Brain Res. 886 (1–2), 237 (2000).

  2. J. M. Bower, Front. Cell. Neurosci. 4, pii:27 (2010).

    Google Scholar 

  3. J. C. Eccles, M. Ito, and J. Szentagothai, The Cerebellum as a Neuronal Machine (Springer-Verlag, Berlin, 1967).

    Book  Google Scholar 

  4. V. G. Shakkottai, M. do Carmo Costa, J. M. Dell’Orco, et al., J. Neurosci. 31 (36), 13002 (2011).

    Article  Google Scholar 

  5. J. T. Walter, K. Alvina, M. D. Womack, et al., Nat. Neurosci. 9 (3), 389 (2006).

    Article  Google Scholar 

  6. W. Pan, W.-Y. Wu, Y.-H. Bing, et al., Pharmacology 103, 82 (2019).

    Article  Google Scholar 

  7. H. Liu, S.-N. Zhao, G.-Y. Zhao, et al., Brain Res. 1560, 1 (2014).

    Article  Google Scholar 

  8. H. S. Swatzwelder, W. W. Anderson, and W. A. Wilson, Epilepsy Res. 2 (4), 239 (1988).

    Article  Google Scholar 

  9. M. J. Gutnick, B. Wolfson, and F. Baldino, Exp. Brain Res. 76 (1), 131 (1989).

    Article  Google Scholar 

  10. M. Saeza, M. Ketzefb, J. Alegre-Cortesa, et al., Neuroscience 381, 115 (2018).

    Article  Google Scholar 

  11. D. A. Sibarov, P. A. Abushik, A. E. Bolshakov, et al., Biol. Membr. 31 (1), 33 (2014).

    Google Scholar 

  12. C. Takayama and Y. Inoue, Anat. Sci. Int. 79, 124 (2004).

    Article  Google Scholar 

  13. J. Altman, J. Comp. Neurol. 145, 399 (1972b

    Article  Google Scholar 

  14. J. Takacs and J. Hamori, J. Neurosci. Res. 38 (5), 515, (1994).

    Article  Google Scholar 

  15. H. Yamanaka, Y. Yanagawa, and K. Obata, Neurosci. Res. 50, 1 (2004).

    Article  Google Scholar 

  16. B. E. McKay and R. W. Turner, J. Physiol. 567 (3), 829 (2005).

    Article  Google Scholar 

  17. M. Gymnopoulos, L. A. Cingolani, P. Pedarzani, et al., J. Comp. Neurol. 522 (5), 1072 (2014).

    Article  Google Scholar 

  18. M. D. Womack and K. Khodakhah, J. Neurosci. 23 (7), 2600 (2003).

    Article  Google Scholar 

  19. T. V. Karelina, Yu. D. Stepanenko, P. A. Abushik, et al., Acta Naturae 8, 4(31), 91 (2016).

  20. P. A. Egorova, T. V. Karelina, O. L. Vlasova, et al., J. Evol. Biochem. Physiol. 50 (2), 114 (2014).

    Article  Google Scholar 

  21. Z. Gao, B. Todorov, C. F. Barrett, et al., J. Neurosci. 32 (44), 15533 (2012).

    Article  Google Scholar 

  22. M. Samson, D. O. Claassen, Neurodegener Dis. 17 (4–5), 155 (2017).

  23. E. V. Mironova, A. A. Evstratova, and S. M. Antonov, J. Neurosci. Methods 163, 1 (2007).

    Article  Google Scholar 

  24. A. Lau and M. Tymianski, Pflugers Arch. 460 (2), 525 (2010).

    Article  Google Scholar 

  25. M. B. Pisu, E. Roda, D. Avella, et al., Neuroscience 129, 655 (2004).

    Article  Google Scholar 

  26. M. Hausser and B. A. Clark, Neuron 19, 665 (1997).

    Article  Google Scholar 

  27. S. Guan, S. Ma, Y. Zhu, et al., Brain Res. 1097 (1), 59 (2006).

    Article  Google Scholar 

  28. Y. H. Chung, C. M. Shin, M. J. Kim, et al., Brain Res. 903 (1–2), 247 (2001).

  29. D. A. Sibarov, J. D. Stepanenko, I. V. Silantiev, et al., J. Mol. Neurosci. 64 (2), 300 (2018).

    Article  Google Scholar 

Download references

Funding

The study was done with a support of the State assignment of IEPHB RAS.

Author information

Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    T. V. Karelina, Y. D. Stepanenko, D. A. Sibarov, P. A. Abushik & S. M. Antonov

Authors
  1. T. V. Karelina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. D. Stepanenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. A. Sibarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. A. Abushik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. M. Antonov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. A. Abushik.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.Statement on the welfare of animals. All applicable international, national and institutional principles for the care and use of animals in the performance of work have been observed.

Additional information

Translated by E. Puchkov

Abbreviations: PCs, Purkinje cells; GABA, γ-aminobutyric acid; SR 95 531, 6-imino-3-(4-methoxyphenyl)-1(6H)-pyrazinobutanic acid hydrobromide (gabazine); SK channels, Ca2+-activated K+ channels of small conductance; NS 309, 6,7-dichloro-1H-indole-2,3-diketone-3-oxime.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karelina, T.V., Stepanenko, Y.D., Sibarov, D.A. et al. Inhibition of GABAergic Transmission as a Model of Hyperactivation of Purkinje Cells in the Rat Cerebellum. BIOPHYSICS 65, 88–94 (2020). https://doi.org/10.1134/S000635092001008X

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S000635092001008X

Search

Navigation