Vol. 35 (2025): Volumen 35
Artículos de Investigación

CellCorticalDisplastic: Educational simulator for the recovery of NMDA receptor desensitization

PDF (Español (España))
  • Marleni Reyes Monreal,
  • María Eugenia Pérez Bonilla,
  • Jessica Quintero Pérez,
  • Arturo Reyes Lazalde,
  • María Beatriz Bernábe-Loranca
Marleni Reyes Monreal
Benemérita Universidad Autónoma de Puebla
María Eugenia Pérez Bonilla
Benemérita Universidad Autónoma de Puebla
Jessica Quintero Pérez
Benemérita Universidad Autónoma de Puebla
Arturo Reyes Lazalde
Facultad de Ciencias Biológicas, Benemérita Universidad Autónoma de Puebla
María Beatriz Bernábe-Loranca
Benemérita Universidad Autónoma de Puebla
DOI: https://doi.org/10.15174/au.2025.4187

Published 2025-06-04

How to Cite

Reyes Monreal, M., Pérez Bonilla, M. E., Quintero Pérez, J., Reyes Lazalde, A., & Bernábe-Loranca, M. B. (2025). CellCorticalDisplastic: Educational simulator for the recovery of NMDA receptor desensitization. Acta Universitaria, 35. https://doi.org/10.15174/au.2025.4187

Abstract

The NMDA (N-methyl-D-aspartate) receptor constitutes a significant component of excitatory synapses. The presence of intractable epilepsy in some patients with cortical dysplasia (CD) underscores the relevance of histological, electrophysiological, and molecular investigations to understand the mechanisms involved. In this context, a simulator based on the work by André et al., aimed at educational objectives, has been conceived. It features a curriculum that introduces students to the topic and allows for virtual practical exercises. The simulator faithfully reproduces the recovery of desensitization in NO-CD cells, apparently normal CD cells, and cytomegalic CD cells, as evidenced in experimental records. The implemented mathematical model allowed for theoretical estimation of internal calcium concentration in the reported experiments.

PDF (Español (España))

References

  1. Akil, H., Balice-Gordon, R., Lopes, D., Koroshetz, W., Posey, S. M., Sherer, T., Sherman, S. M., & Thiels, E. (2016). Neuroscience training for the 21st Century. Neuron, 90(5), 917–926. https://doi.org/10.1016/j.neuron.2016.05.030
  2. Altimus, C. M., Marlin, B. J., Charalambakis, N. E., Colón-Rodriquez, A., Glover, E. J., Izbicki, P., Johnson, A., Lourenco, M. V., Makinson, R. A., McQuail, J., Obeso, I., Padilla-Coreano, N., & Wells, M. F. (2020). The next 50 years of neuroscience. Journal of Neuroscience, 40(21), 101–106. https://doi.org/10.1523/JNEUROSCI.0103-20.2020
  3. André, V. M., Flores-Hernández, J., Cepeda, C., Starling, A. J., Nguyen, S., Lobo, M. K., Vinters, H. V., Levine, M. S., & Mathern, G. W. (2004). NMDA receptor alterations in neurons from pediatric cortical dysplasia tissue. Cerebral Cortex, 14(6), 634–646. https://doi.org/10.1093/cercor/bhh024
  4. Aneja, S., & Jain, P. (2014). Refractory epilepsy in children. The Indian Journal of Pediatrics, 81, 1063–1072. https://doi.org/10.1007/s12098-014-1533-1
  5. Av-Ron, E., Byrne, M. J., Byrne, J. H., & Baxter, D. A. (2008). SNNAP: a tool for teaching neuroscience. Brains, Minds and Media, 3, 1–11. https://www.brains-minds-media.org/archive/1408/bmm1408.pdf
  6. Berkefeld, H., Fakler, B., & Schulte, U. (2010). Ca2+-activated K+ channels: from protein complexes to function. Physiological Reviews, 90(4), 1437–1459. https://doi.org/10.1152/physrev.00049.2009
  7. Bower, J. M., Beeman, D., Bower, J. M., & Beeman, D. (1995). Neural Modeling with GENESIS. The Book of GENESIS. http://genesis-sim.org/GENESIS/bog/bog.html
  8. Carnevale, N. T., & Hines, M. L. (2006). The NEURON book. Cambridge University Press. https://doi.org/10.1017/CBO9780511541612
  9. Cepeda, C., André, V. M., Levine, M. S., Salamon, N., Miyata, H., Vinters, H. V., & Mathern, G. W. (2006). Epileptogenesis in pediatric cortical dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy & Behavior, 9(2), 219–235. https://doi.org/10.1016/j.yebeh.2006.05.012
  10. Cepeda, C., André, V. M., Wu, N., Yamazaki, I., Uzgil, B., Vinters, H. V., Levine, M. S., & Mathern, G. W. (2007). Immature neurons and GABA networks may contribute to epileptogenesis in pediatric cortical dysplasia. Epilepsia, 48(5), 79–85. https://doi.org/10.1111/j.1528-1167.2007.01293.x
  11. Cepeda, C., Hurst, R. S., Flores-Hernández, J., Hernández-Echeagaray, E., Klapstein, G. J., Boylan, M. K., Calvert, C. R., Jocoy, E. L., Nguyen, O. K., André, V. M., Vinters, H. V., Ariano, M. A., Levine, M. S., & Mathern, G. W. (2003). Morphological and electrophysiological characterization of abnormal cell types in pediatric cortical dysplasia. Journal of Neuroscience Research, 72(4), 472–486. https://doi.org/10.1002/jnr.10604
  12. Crino, P. B. (2015). Focal cortical dysplasia. Seminars in Neurology, 35(03), 201-208. https://doi.org/10.1055/s-0035-1552617
  13. Diwakar, S., Parasuram, H., Medini, C., Raman, R., Nedungadi, P., Wiertelak, E., Srivastava, S., Achuthan, K., & Nair, B. (2014). Complementing neurophysiology education for developing countries via cost-effective virtual labs: case studies and classroom scenarios. Journal of Undergraduate Neuroscience Education, 12(2), 130–139. https://pmc.ncbi.nlm.nih.gov/articles/PMC3970995/
  14. Fan, X., & Markram, H. (2019). A brief history of simulation neuroscience. Frontiers in Neuroinformatics, 13, 1–28. https://doi.org/10.3389/fninf.2019.00032
  15. García, D., Álvarez, E., González, E., & Guzmán, D. (2019). La nueva Licenciatura en Neurociencias de la UNAM: lecciones aprendidas. Investigación en Educación Médica, 8(29), 104–109. https://doi.org/10.22201/facmed.20075057e.2019.29.18104
  16. Gerstner, W., Sprekeler, H., & Deco, G. (2012). Theory and simulation in neuroscience. Science, 338(6103), 60–65. https://doi.org/10.1126/science.1227356
  17. Goldman, M. S., & Fee, M. S. (2017). Computational training for the next generation of neuroscientists. Current Opinion in Neurobiology, 46, 25–30. https://doi.org/10.1016/j.conb.2017.06.007
  18. Guo, H., Camargo, L. M., Yeboah, F., Digan, M. E., Niu, H., Pan, Y., Reiling, S., Soler-Llavina, G., Weihofen, W. A., Wang, H. R., Shanker, Y. G., Stams, T., & Bill, A. (2017). A NMDA-receptor calcium influx assay sensitive to stimulation by glutamate and glycine/D-serine. Scientific Reports, 7(11608), 1–13. https://doi.org/10.1038/s41598-017-11947-x
  19. Hernández-Carrillo, F., Campillo, M., & Sánchez-Mendiola, M. (2018). Investigación traslacional en ciencias de la salud: implicaciones educativas y retos. Investigación en Educación Médica, 7(28), 85–97. https://doi.org/10.22201/facmed.20075057e.2018.28.18146
  20. Herta, J., & Dorfer, C. (2019). Surgical treatment for refractory epilepsy. Journal of Neurosurgical Sciences, 63(1), 50–60. https://doi.org/10.23736/S0390-5616.18.04448-X
  21. Horrigan, L. A. (2018). Tackling the threshold concepts in physiology: What is the role of the laboratory class?. Advances in Physiology Education, 42(3), 507–515. https://doi.org/10.1152/advan.00123.2017
  22. Iacobucci, G. J., & Popescu, G. K. (2017). Resident calmodulin primes NMDA receptors for Ca2+-dependent inactivation. Biophysical Journal, 113(10), 2236–2248. https://doi.org/10.1016/j.bpj.2017.06.035
  23. Inglebert, Y., & Debanne, D. (2021). Calcium and spike timing-dependent plasticity. Frontiers in Cellular Neurophysiology, 15, 1–9. https://doi.org/10.3389/fncel.2021.727336
  24. Jahr, C. E., & Stevens, C. F. (1990a). A quantitative description of NMDA receptor-channel kinetic behavior. The Journal of Neuroscience, 10(6), 1830–1837. https://doi.org/10.1523/JNEUROSCI.10-06-01830.1990
  25. Jahr, C. E., & Stevens, C. F. (1990b). Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. The Journal of Neuroscience, 10(9), 3178–3182. https://doi.org/10.1523/JNEUROSCI.10-09-03178.1990
  26. Lorenz, S., & Egelhaaf, M. (2008). Curricular integration of simulations in neuroscience. Brains, Minds & Media, 3, 1-20. https://www.brains-minds-media.org/archive/1427/bmm1427.pdf
  27. McDougal, R. A., Bulanova, A. S., & Lytton, W. W. (2016). Reproducibility in computational neuroscience models and simulations. IEEE Transactions on Biomedical Engineering, 63(10), 2021–2035. https://doi.org/10.1109/TBME.2016.2539602
  28. Meldolesi, J. (2001). Rapidly exchanging Ca2+ stores in neurons: molecular, structural and functional properties. Progress in Neurobiology, 65(3), 309–338. https://doi.org/10.1016/S0301-0082(01)00004-1
  29. Mohsin, S. N., Grezenko, H., Khan, S., Eshete, F. D., Shrestha, S., Kamran, M., Affaf, M., Jama, A., Gasim, R. W., Ahmad, D. Z., Yadav, I., Arif, S., K. C., A., & Khaliq, A. S. (2023). Bridging development and disruption: comprehensive insights into focal cortical dysplasia and epileptic management. Cureus, 15(9), e45996. https://doi.org/10.7759/cureus.45996
  30. Oprisan, S. A. (2022). Interdisciplinary curriculum for computational neuroscience at primarily undergraduate institutions. Journal of Computational Science, 61, 1–21. https://doi.org/10.1016/j.jocs.2022.101642
  31. Reyes-Monreal, M., Quintero-Pérez, J., Pérez-Bonilla, M. E., Reyes-Lazalde, A., & Flores-Hernández, J. (2022). Lab-NMDAR: simuladores de la electrofisiología básica del receptor NMDA. Acta Universitaria, 32, 1-23. https://doi.org/10.15174/au.2022.3597
  32. Reyes-Monreal, M., Quintero-Pérez, J., Pérez-Bonilla, M. E., Pérez-Escalera, M., & Reyes-Lazalde, A. (2024). Theoretical calculation of NMDA receptor desensitization and intracellular calcium determination through simulation. https://doi.org/10.30574/ijsra.2024.11.1.0020
  33. Sibarov, D. A., & Antonov, S. M. (2018). Calcium-dependent desensitization of NMDA receptors. Biochemistry (Moscow), 83(10), 1173–1183. https://doi.org/10.1134/S0006297918100036
  34. Szydlowska, K., & Tymianski, M. (2010). Calcium, ischemia and excitotoxicity. Cell Calcium, 47(2), 122–129. https://doi.org/10.1016/j.ceca.2010.01.003
  35. Van Vugt, B., van Kerkoerle, T., Vartak, D., & Roelfsema, P. R. (2020). The contribution of AMPA and NMDA receptors to persistent firing in the dorsolateral prefrontal cortex in working memory. Journal of Neuroscience, 40(12), 2458–2470. https://doi.org/10.1523/JNEUROSCI.2121-19.2020
  36. Vyklický, L. (1993). Calcium‐mediated modulation of N‐methyl‐D‐aspartate (NMDA) responses in cultured rat hippocampal neurones. The Journal of Physiology, 470(1), 575–600. https://doi.org/10.1113/jphysiol.1993.sp019876

Most read articles by the same author(s)