New technology in experimental neurobiology: neuronal networks coupled with multielectrode array

Cover Page


Cite item

Full Text

Abstract

Multielectrode arraуs (MEA) as the recording and stimulating system for self-organizing, functionally heterogeneous neuronal network formed by developing CNS cells in vitro is a new, unique technology for investigation of mechanisms of pathological neurodestructive processes and for searching the means of their pharmacological corrections. The principal advantages of the MEA are the precise noninvasive long-term network stimulation and measurement of the electric signals, pharmacological testing and drug screening, optical structural and functional imaging of metabolic ionic current into neurons and glial cells using confocal laser scanning microscopy. The brain cells and tissues coupled in vitro with MEA enables neuroprotective and/or neurotoxic drug testing in different models of the central nervous system pathological states. Data-intensive part, good reproducibility and quantitative assessment capability make it possible to relate the neuron networks cultured to the MEA with biosensors, allowing to perform effective pharmacological screening in vitro for the models of ischemia, trauma, epilepsy, Alzheimer’s disease, etc.

 

About the authors

I. V. Mukhina

Nizhny Novgorod State Medical Academy

Email: haspekleon@mail.ru
Россия, Nizhny Novgorod

Leonid G. Khaspekov

Research Center of Neurology

Author for correspondence.
Email: khaspekleon@mail.ru
Россия, Moscow

References

  1. Мухина И.В., Казанцев В.Б., Хаспеков Л.Г. и др. Мультиэлектродные матрицы – новые возможности в исследовании пластичности нейрональной сети. Совр. технол. в медицине 2009; 1: 6–15.
  2. Ahuja T.K., Mielke J.G., Comas T. et al. Hippocampal slice cultures integrated with multi-electrode arrays: a model for study of long-term drug effects on synaptic activity. Drug Devel. Res. 2007; 68: 84–93.
  3. Baldelli P., Fassio A., Valtorta F., Benfenati F. Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. J. Neurosci. 2007; 27: 13520–13531.
  4. Bal-Price A.K., Sunol C., Weiss D.G. et al. Application of in vitro neurotoxicity testing for regulatory purposes: Symposium III summary and research needs. Neurotoxicology 2008; 29: 520–531.
  5. Ban J., Bonifazi P., Pinato G. et al. Embryonic stem cell-derived neurons form functional networks in vitro. Stem Cells 2007; 25: 738–749.
  6. Benilova I., Kuperstein I., Broersen K. et al. MEA neurosensor, the tool for synaptic activity detection: acute amyloid-b oligomers synaptotoxicity study. In: IFMBE Proceedings, O. Dössel and W.C. Schlegel (eds.). Springer, 2009: 314–316.
  7. Brette R., Rudolph M., Carnevale T. et al. Simulation of networks of spiking neurons: A review of tools and strategies. J. Comput. Neurosci. 2007; 23: 349–398.
  8. Chen Y., Guo C., Lim L. et al. Compact microelectrode array system: tool for in situ monitoring of drug effects on neurotransmitter release from neural cells. Anal. Chem. 2008; 80: 1133–1140.
  9. Chiappalone M., Boveb M., Vato A. et al. Dissociated cortical networks show spontaneously correlated activity patterns during in vitro development. Brain Res. 2006; 1093: 41–53.
  10. Chiappalone M., Novellinoa A., Vajda I. et al. Burst detection algorithms for the analysis of spatio-temporal patterns in cortical networks of neurons. Neurocomputing 2005; 65–66: 653–662.
  11. Chiappalone M., Vato A., Berdondini L. et al. Network dynamics and synchronous activity in cultured cortical neurons. Int. J. Neur. Syst. 2007; 17: 87–103.
  12. Chiappalone M., Vato A., Tedesco M. et al. Networks of neurons coupled to microelectrode arrays: a neuronal sensory system for pharmacological applications. Biosens. Bioelectr. 2003; 18: 627–634.
  13. Chien C.B., Pine J. Voltage-sensitive dye recording of action potentials and synaptic potentials from sympathetic microcultures. Biophys. J. 1991; 60: 697–711.
  14. Egert U. Networks on chips: Spatial and temporal activity dynamics of functional networks in brain slices and cardiac tissue. In: BioMEM, G. Urban (ed.), Springer 2006: 309–349.
  15. Eytan D., Marom S. Dynamics and effective topology underlying synchronization in networks of cortical neurons. J. Neurosci. 2006; 26: 8465–8476.
  16. Gopal K.V., Miller B.R., Gross G.W. Acute and sub-chronic functional neurotoxicity of methylphenidate on neural networks in vitro. J. Neural Transm. 2007; 114: 1365–1375.
  17. Gortz P., Opatz J., Siebler M. et al. Transient reduction of spontaneous neuronal network activity by sublethal amyloid b (1–42) peptide concentrations. Ibid 2009; 116: 351–355.
  18. Gramowski A., Jugelt K., Weiss D.G., Gross G.W. Substance identification by quantitative characterization of oscillatory activity in murine spinal cord networks on microelectrode arrays. Eur. J. Neurosci. 2004; 19: 2815–2825.
  19. Gross G.W., Harsch A., Rhoades B.K., Gopel W. Odor, drug and toxin analysis with neuronal networks in vitro:extracellular array recording of network responses. Biosens. Bioelectr. 1997; 12: 373–393.
  20. Heikkilä T.J., Ylä-Outinen L., Tanskanen J.M.A. et al. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro. Exp. Neurol. 2009; 218: 109–116.
  21. Hill A.J., Jones N.A., Williams C.M. et al. Development of multielectrode array screening for anticonvulsants in acute rat brain slices. J. Neurosci. Meth. 2010; 185: 246–256.
  22. Hill A.J., Weston S.E., Jones N.A. D9-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia 2010: epub ahead.
  23. Illes S., Fleischer W., Siebler M. et al. Development and pharmacological modulation of embryonic stem cell-derived neuronal network activity. Exp. Neurol. 2007; 207: 171–176.
  24. Illes S., Theiss S., Hartung H.-P. et al. Niche-dependent development of functional neuronal networks from embryonic stem cellderived neural populations. BMC Neurosci. 2009; 10: 93–109.
  25. Jones N.A., Hill A.J., Smith I. et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J. Pharm. Exp. Ther. 2010; 332: 569–577.
  26. Kamioka H., Jimbo Y., Charlety P.J., Kawana A. Planar electrode arrays for long-term measurement of neuronal firing in cultured cortical slices. Cellular Eng. 1997; 2: 148–153.
  27. Kang G., Lee J.-H., Leeb C.-S., Nam Y. Agarose microwell based neuronal microcircuit arrays on microelectrode arrays for high throughput drug testing. Lab. Chip. 2009; 9: 3236–3242.
  28. Karkar K.M., Garcia P.A., Bateman L.M. et al. Focal cooling suppresses spontaneous epileptiform activity without changing the cortical motor threshold. Epilepsia 2002; 43: 932–935.
  29. Keefer E.W., Gramowski A., Gross G.W. NMDA receptor-dependent periodic oscillations in cultured spinal cord networks. J. Neurophysiol. 2001; 86: 3030–3042.
  30. Linke S., Goertz P., Baader S.L. et al. Aldolase C/Zebrin II is released to the extracellular space after stroke and inhibits the etwork activity of cortical neurons. Neurochem. Res. 2006; 31: 1297–1303.
  31. Madhavan R., Chao Z.C., Potter S.M. Plasticity of recurring spatiotemporal activity patterns in cortical networks. Phys. Biol. 2007; 4: 181–193.
  32. McIntyre A.L., Fergusson A.D., Hebert C.P. et al. Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. JAMA 2003; 22: 2992–2999.
  33. Nimmrich V., Grimm C., Draguhn A. et al. Amyloid beta oligomers (A beta (1–42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J. Neurosci.2008; 28: 788–797.
  34. O’Shaughnessy T.J., Liu J.L., Ma W. Passaged neural stem cellderived neuronal networks for a portable biosensor. Biosens. Bioelectr. 2009; 24: 2365–2370.
  35. Pine J. Recording action potentials from cultured neurons with extracellular microcircuit electrodes. J. Neurosci. Meth. 1980; 2: 19–31.
  36. Pettit D.L., Shao Z., Yakel J.L. Beta-amyloid (1–42) peptide directly modulates nicotinic receptors in the rat hippocampal slice. J. Neurosci. 2001; 21: RC120: 1–5.
  37. Pizzi R.M.R., Cino G., Gelain F. et al. Learning in human neural networks on microelectrode arrays. Biosystems 2007; 88: 1–15.
  38. Pizzi R.M.R., Rossetti D., Cino G. et al. A cultured human neural network operates a robotic actuator. Ibid 2009; 95: 137–144.
  39. Prado G.R., Ross J.D., DeWeerth S.P., LaPlaca M.C. Mechanical trauma induces immediate changes in neuronal network activity. J. Neural Eng. 2005; 2: 148–158.
  40. Regehr W.G., Pine J., Cohan C.S. et al. Sealing cultured neurons to embedded dish electrodes facilitates long-term stimulation and recording. J. Neurosci. Meth. 1989; 30: 91–106.
  41. Rubinsky L., Raichman N., Baruch I. et al. Study of hypothermia on cultured neuronal networks using multi-electrode arrays. Ibid 2007; 160: 288–293.
  42. Rubinsky L., Raichman N., Lavee J. Spatio-temporal motifs `remembered’ in neuronal networks following profound hypothermia. Neural Netw. 2008; 21: 1232–1237.
  43. Ruaro M.E., Bonifazi P., Torre V. Toward the neurocomputer: image processing and pattern recognition with neuronal cultures. IEEE Trans. Biomed. Eng. 2005; 52: 371–383.
  44. Shimono K., Baudry M., Panchenko V., Taketani M. Chronic multichannel recordings from organotypic hippocampal slice cultures: protection from excitotoxic effects of NMDA by noncompetitive NMDA antagonists. J. Neurosci. Meth. 2002; 120: 193–202.
  45. Srinivas K.V., Jain R., Saurav S., Sikdar S.K. Small-world network topology of hippocampal neuronal network is lost, in an in vitro glutamate injury model of epilepsy. Eur. J. Neurosci. 2007; 25: 3276–3286.
  46. Shtark M.B., Ratushnyak A.S., Voskresenskaya L.V., Olenev S.N. A multielectrode perfusion chamber for tissue culture research. Bull. Exp. Biol. Med. 1974; 78; 1090–1092.
  47. Sun D.A., Sombati S., Blair R.E., DeLorenzo R.J. Long-lasting alterations in neuronal calcium homeostasis in an in vitro model of stroke induced epilepsy. Cell Calcium, 2004; 35: 155–163.
  48. Takayama Y., Moriguchi H., Kotani K., Jimbo Y. Spontaneous calcium transients in cultured cortical networks during development. IEEE Trans. Biomed. Eng. 2009; 56: 2949–2956.
  49. Thomas C.A., Springer P.A., Loeb G.E. et al. A miniature microelectrode array to monitor the bioelectric activity of cultured cells. Exp. Cell Res. 1972; 74: 61–66.
  50. Van Pelt J., Vajda I., Wolters P.S. et al. Dynamics and plasticity in developing neuronal networks in vitro. Prog. Brain Res. 2005; 147: 173–188.
  51. Varghese K., Molnar P., Das M. et al. A new target for amyloid beta toxicity validated by standard and high-throughput electrophysiology. PLoS One 2010; 5: e8643.
  52. Venkitaramani D.V., Chin J., Netzer W.J. et al. Beta-amyloid modulation of synaptic transmission and plasticity. J. Neurosci. 2007; 27: 11832–11837.
  53. Wagenaar D.A., Pine J., Potter S.M. An extremely rich repertoire of bursting patterns during the development of cortical cultures. BMC Neurosci. 2006; 7: 11–29.
  54. Wahl A.-S., Buchthal B., Rode F. Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors. Neurosci. 2009; 158: 344–352.
  55. Wang Q., Rowan M.J., Anwyl R. Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide. J. Neurosci. 2004; 24: 6049–6056.
  56. Wheeler B.C., Novak J.L. Current source density estimation using microelectrode array data from the hippocampal slice preparation. IEEE Trans. Biomed. Eng. 1986; 33: 1204–1212.
  57. Xiang G., Pan L., Huange L. et al. Microelectrode array-based system for neuropharmacological applications with cortical neurons cultured in vitro. Biosens. Bioelectr. 2007; 22: 2478–2484.
  58. Yang X.F., Chang J.H., Rothman S.M. Long-lasting anticonvulsant effect of focal cooling on experimental neocortical seizures. Epilepsia 2003; 44: 1500–1505.
  59. Yu Z., Graudejus O., Tsay C. et al. Monitoring hippocampus electrical activity in vitro on an elastically deformable microelectrode array. J. Neurotrauma 2009; 26: 1135–1145.
  60. Yu Z., Tsay C., Lacour S.P. et al. Stretchable microelectrode arrays – a tool for discovering mechanisms of functional deficits underlying traumatic brain injury and interfacing neurons with neuroprosthetics. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2006; Suppl.: 6732–6735.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2010 Mukhina I.V., Khaspekov L.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies