Skip to main content
SpringerLink
Log in

Sub-Second Measurements of Glutamate and Other Neurotransmitter Signaling Using Enzyme-Based Ceramic Microelectrode Arrays

  • Protocol
  • First Online:
Microelectrode Biosensors

Part of the book series: Neuromethods ((NM,volume 80))

Abstract

We have set out to develop a novel, implantable microelectrode array that has the capabilities to detect neurotransmitters with enhanced sensitivity, selectivity, and temporal sampling capabilities compared to other current technologies. We have shown that this device maintains recording performance during chronic measurements of extracellular neurotransmitter levels for at least 7 days postimplantation, single-unit neuronal activity for as long as 6 months, and provides enhanced biocompatibility compared to current technologies. As we continue to refine and improve our recording capability, we are able to incorporate the chronic microelectrode array technology into multimodal experimental paradigms, such as behavioral testing, pharmacological intervention (local and systemic), or combined measurements of neurotransmitter levels and neuronal activity (local field potential). Furthermore, the improvements made with the microelectrode technology discussed in this chapter have the potential to conduct longitudinal analyses that can benefit a wide range of translational efforts, including studies on learning and memory, aging, neurodegenerative disease progression, and traumatic brain injury neuropathology.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kennedy RT, Thompson JE, Vickroy TW (2002) In vivo monitoring of amino acids by direct sampling of brain extracellular fluid at ultralow flow rates and capillary electrophoresis. J Neurosci Methods 114:39–49

    Article  CAS  PubMed  Google Scholar 

  2. Watson CJ, Venton BJ, Kennedy RT (2006) In vivo measurements of neurotransmitters by microdialysis sampling. Anal Chem 78:1391–1399

    Article  PubMed  Google Scholar 

  3. Timmerman W, Westerink BH (1997) Brain microdialysis of GABA and glutamate: what does it signify? Synapse 27:242–261

    Article  CAS  PubMed  Google Scholar 

  4. Lada MW, Vickroy TW, Kennedy RT (1997) High temporal resolution monitoring of glutamate and aspartate in vivo using microdialysis on-line with capillary electrophoresis with laser-induced fluorescence detection. Anal Chem 69:4560–4565

    Article  CAS  PubMed  Google Scholar 

  5. Tucci S, Rada P, Sepulveda MJ, Hernandez L (1997) Glutamate measured by 6-s resolution brain microdialysis: capillary electrophoretic and laser-induced fluorescence detection application. J Chromatogr B Biomed Sci Appl 694:343–349

    Article  CAS  PubMed  Google Scholar 

  6. Rossell S, Gonzalez LE, Hernandez L (2003) One-second time resolution brain microdialysis in fully awake rats. Protocol for the collection, separation and sorting of nanoliter dialysate volumes. J Chromatogr B Analyt Technol Biomed Life Sci 784:385–393

    Article  CAS  PubMed  Google Scholar 

  7. Clapp-Lilly KL, Roberts RC, Duffy LK, Irons KP, Hu Y, Drew KL (1999) An ultrastructural analysis of tissue surrounding a microdialysis probe. J Neurosci Methods 90:129–142

    Article  CAS  PubMed  Google Scholar 

  8. Westerink RH (2004) Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity. Neurotoxicology 25:461–470

    Article  CAS  PubMed  Google Scholar 

  9. Suaud-Chagny MF, Cespuglio R, Rivot JP, Buda M, Gonon F (1993) High sensitivity measurement of brain catechols and indoles in vivo using electrochemically treated carbon-fiber electrodes. J Neurosci Methods 48:241–250

    Article  CAS  PubMed  Google Scholar 

  10. Hu Y, Mitchell KM, Albahadily FN, Michaelis EK, Wilson GS (1994) Direct measurement of glutamate release in the brain using a dual enzyme-based electrochemical sensor. Brain Res 659:117–125

    Article  CAS  PubMed  Google Scholar 

  11. Oldenziel WH, Dijkstra G, Cremers TI, Westerink BH (2006) In vivo monitoring of extracellular glutamate in the brain with a microsensor. Brain Res 1118:34–42

    Article  CAS  PubMed  Google Scholar 

  12. Tian F, Gourine AV, Huckstepp RT, Dale N (2009) A microelectrode biosensor for real time monitoring of L-glutamate release. Anal Chim Acta 645:86–91

    Article  CAS  PubMed  Google Scholar 

  13. Rutherford EC, Pomerleau F, Huettl P, Stromberg I, Gerhardt GA (2007) Chronic second-by-second measures of L-glutamate in the central nervous system of freely moving rats. J Neurochem 102:712–722

    Article  CAS  PubMed  Google Scholar 

  14. Hascup KN, Hascup ER, Pomerleau F, Huettl P, Gerhardt GA (2008) Second-by-second measures of L-glutamate in the prefrontal cortex and striatum of freely moving mice. J Pharmacol Exp Ther 324:725–731

    Article  CAS  PubMed  Google Scholar 

  15. Hascup ER, Hascup KN, Stephens M, Pomerleau F, Huettl P, Gratton A, Gerhardt GA (2010) Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex. J Neurochem 115:1608–1620

    Article  CAS  PubMed  Google Scholar 

  16. Hascup ER, af Bjerken S, Hascup KN, Pomerleau F, Huettl P, Stromberg I, Gerhardt GA (2009) Histological studies of the effects of chronic implantation of ceramic-based microelectrode arrays and microdialysis probes in rat prefrontal cortex. Brain Res 1291:12–20

    Article  CAS  PubMed  Google Scholar 

  17. Zhang H, Lin SC, Nicolelis MA (2010) Spatiotemporal coupling between hippocampal acetylcholine release and theta oscillations in vivo. J Neurosci 30:13431–13440

    Article  CAS  PubMed  Google Scholar 

  18. Zhang H, Lin SC, Nicolelis MA (2009) Acquiring local field potential information from amperometric neurochemical recordings. J Neurosci Methods 179:191–200

    Article  CAS  PubMed  Google Scholar 

  19. Burmeister JJ, Moxon K, Gerhardt GA (2000) Ceramic-based multisite microelectrodes for electrochemical recordings. Anal Chem 72:187–192

    Article  CAS  PubMed  Google Scholar 

  20. Burmeister JJ, Pomerleau F, Palmer M, Day BK, Huettl P, Gerhardt GA (2002) Improved ceramic-based multisite microelectrode for rapid measurements of L-glutamate in the CNS. J Neurosci Methods 119:163–171

    Article  CAS  PubMed  Google Scholar 

  21. Hascup KN, Rutherford EC, Quintero JE, Day BK, Nickell JR, Pomerleau F, Huettl P, Burmeister JJ, Gerhardt GA (2006) Second-by-second measures of L-glutamate and other neurotransmitters using enzyme-based microelectrode arrays. In: Michael AC, Borland LM (eds) Electrochemical methods for neuroscience. CRC, Boca Raton, FL, pp 407–450

    Chapter  Google Scholar 

  22. Burmeister JJ, Gerhardt GA (2001) Self-referencing ceramic-based multisite microelectrodes for the detection and elimination of interferences from the measurement of L-glutamate and other analytes. Anal Chem 73:1037–1042

    Article  CAS  PubMed  Google Scholar 

  23. Nickell J, Pomerleau F, Allen J, Gerhardt GA (2005) Age-related changes in the dynamics of potassium-evoked L-glutamate release in the striatum of Fischer 344 rats. J Neural Transm 112:87–96

    Article  CAS  PubMed  Google Scholar 

  24. Gerhardt GA, Burmeister JJ (2000) In vivo voltammetry for chemical analysis of the nervous system. In: Meyers RA (ed) Encyclopedia of analytical chemistry: instrumentation and applications. Wiley, Chichester

    Google Scholar 

  25. Paxinos G, Watson C (2008) The rat brain in stereotaxic coordinates: compact, 6th edn. Academic, New York, NY

    Google Scholar 

  26. Day BK, Pomerleau F, Burmeister JJ, Huettl P, Gerhardt GA (2006) Microelectrode array studies of basal and potassium-evoked release of L-glutamate in the anesthetized rat brain. J Neurochem 96:1626–1635

    Article  CAS  PubMed  Google Scholar 

  27. Liachenko S, Tang P, Somogyi GT, Xu Y (1998) Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked glutamate and GABA release from mouse cerebrocortical slices. Br J Pharmacol 123:1274–1280

    Article  CAS  PubMed  Google Scholar 

  28. Liachenko S, Tang P, Somogyi GT, Xu Y (1999) Concentration-dependent isoflurane effects on depolarization-evoked glutamate and GABA outflows from mouse brain slices. Br J Pharmacol 127:131–138

    Article  CAS  PubMed  Google Scholar 

  29. Adams RN (1990) In vivo electrochemical measurements in the CNS. Prog Neurobiol 35:297–311

    Article  CAS  PubMed  Google Scholar 

  30. Martin KF, Marsden CA (1987) In vivo electrochemistry–principles and applications. Life Sci 41:865–868

    Article  CAS  PubMed  Google Scholar 

  31. Melendez RI, Vuthiganon J, Kalivas PW (2005) Regulation of extracellular glutamate in the prefrontal cortex: focus on the cystine glutamate exchanger and group I metabotropic glutamate receptors. J Pharmacol Exp Ther 314:139–147

    Article  CAS  PubMed  Google Scholar 

  32. Ballini C, Corte LD, Pazzagli M, Colivicchi MA, Pepeu G, Tipton KF, Giovannini MG (2008) Extracellular levels of brain aspartate, glutamate and GABA during an inhibitory avoidance response in the rat. J Neurochem 106:1035–1043

    Article  CAS  PubMed  Google Scholar 

  33. Clinckers R, Gheuens S, Smolders I, Meurs A, Ebinger G, Michotte Y (2005) In vivo modulatory action of extracellular glutamate on the anticonvulsant effects of hippocampal dopamine and serotonin. Epilepsia 46:828–836

    Article  CAS  PubMed  Google Scholar 

  34. Giovannini MG, Rakovska A, Benton RS, Pazzagli M, Bianchi L, Pepeu G (2001) Effects of novelty and habituation on acetylcholine. GABA, and glutamate release from the frontal cortex and hippocampus of freely moving rats. Neuroscience 106:43–53

    Article  CAS  PubMed  Google Scholar 

  35. Segovia G, Yague AG, Garcia-Verdugo JM, Mora F (2006) Environmental enrichment promotes neurogenesis and changes the extracellular concentrations of glutamate and GABA in the hippocampus of aged rats. Brain Res Bull 70:8–14

    Article  CAS  PubMed  Google Scholar 

  36. Ueda Y, Tsuru N (1995) Simultaneous monitoring of the seizure-related changes in extracellular glutamate and gamma-aminobutyric acid concentration in bilateral hippocampi following development of amygdaloid kindling. Epilepsy Res 20:213–219

    Article  CAS  PubMed  Google Scholar 

  37. Bungay PM, Newton-Vinson P, Isele W, Garris PA, Justice JB (2003) Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma. J Neurochem 86:932–946

    Article  CAS  PubMed  Google Scholar 

  38. Rice ME, Cragg SJ (2008) Dopamine spillover after quantal release: rethinking dopamine transmission in the nigrostriatal pathway. Brain Res Rev 58:303–313

    Article  CAS  PubMed  Google Scholar 

  39. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  CAS  PubMed  Google Scholar 

  40. Nickell J, Salvatore MF, Pomerleau F, Apparsundaram S, Gerhardt GA (2007) Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. Neurobiol Aging 28:1737–1748

    Article  CAS  PubMed  Google Scholar 

  41. Stephens ML, Quintero JE, Pomerleau F, Huettl P, Gerhardt GA (2009) Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus. Neurobiol Aging 32:811–820

    Article  PubMed  Google Scholar 

  42. Dash MB, Douglas CL, Vyazovskiy VV, Cirelli C, Tononi G (2009) Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states. J Neurosci 29:620–629

    Article  CAS  PubMed  Google Scholar 

  43. Hulbert SF, Morrison SJ, Klawitter JJ (1972) Tissue reaction to three ceramics of porous and non-porous structures. J Biomed Mater Res 6:347–374

    Article  CAS  PubMed  Google Scholar 

  44. Biran R, Martin DC, Tresco PA (2007) The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. J Biomed Mater Res A 82:169–178

    PubMed  Google Scholar 

  45. Biran R, Martin DC, Tresco PA (2005) Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp Neurol 195:115–126

    Article  CAS  PubMed  Google Scholar 

  46. Turner KL, Doherty MK, Heering HA, Armstrong FA, Reid GA, Chapman SK (1999) Redox properties of flavocytochrome c3 from Shewanella frigidimarina NCIMB400. Biochemistry 38:3302–3309

    Article  CAS  PubMed  Google Scholar 

  47. Turner JA, Lee JS, Martinez O, Medlin AL, Schandler SL, Cohen MJ (2001) Somatotopy of the motor cortex after long-term spinal cord injury or amputation. IEEE Trans Neural Syst Rehabil Eng 9:154–160

    Article  CAS  PubMed  Google Scholar 

  48. Turner JN, Shain W, Szarowski DH, Andersen M, Martins S, Isaacson M, Craighead H (1999) Cerebral astrocyte response to micromachined silicon implants. Exp Neurol 156:33–49

    Article  CAS  PubMed  Google Scholar 

  49. Leung BK, Biran R, Underwood CJ, Tresco PA (2008) Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry. Biomaterials 29:3289–3297

    Article  CAS  PubMed  Google Scholar 

  50. Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W (2003) Brain responses to micro-machined silicon devices. Brain Res 983:23–35

    Article  CAS  PubMed  Google Scholar 

  51. Spataro L, Dilgen J, Retterer S, Spence AJ, Isaacson M, Turner JN, Shain W (2005) Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex. Exp Neurol 194:289–300

    Article  CAS  PubMed  Google Scholar 

  52. Polikov VS, Tresco PA, Reichert WM (2005) Response of brain tissue to chronically implanted neural electrodes. J Neurosci Methods 148:1–18

    Article  PubMed  Google Scholar 

  53. Rousche PJ, Normann RA (1998) Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex. J Neurosci Methods 82:1–15

    Article  CAS  PubMed  Google Scholar 

  54. Talauliker PM, Price DA, Burmeister JJ, Nagari S, Quintero JE, Gerhardt GA (2011) Ceramic based microelectrode arrays: recording surface characteristics and topographical analysis. J Neurosci Methods 198:222–229

    Article  CAS  PubMed  Google Scholar 

  55. Jung E, Manessis D, Neumann A, Böttcher L, Braun T, Bauer J, Reichl H, Iafelice B, Destro F, Gambari R (2008) Lamination and laser structuring for a microwell array. Microsyst Technol 14:5

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada

    Erin R. Hascup, Kevin N. Hascup & Alain Gratton

  2. Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, Lexington, KY, USA

    Pooja M. Talauliker

  3. Anatomy & Neurobiology, Morris K. Udall Parkinson’s Disease Research Center of Excellence, Center for Microelectrode Technology, College of Medicine, University of Kentucky, Lexington, KY, USA

    David A. Price, Francois Pomerleau, Jorge E. Quintero, Peter Huettl & Greg A. Gerhardt

  4. Department of Integrative Medical Biology, Umeå University, Umeå, Sweden

    Ingrid Strömberg

Authors
  1. Erin R. Hascup
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin N. Hascup
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pooja M. Talauliker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David A. Price
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francois Pomerleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jorge E. Quintero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Huettl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alain Gratton
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ingrid Strömberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Greg A. Gerhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Faculté de médecine, CRNL, Université Claude Bernard Lyon I, Avenue Rockefeller 8, Lyon, 69373, France

    Stéphane Marinesco

  2. School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom

    Nicholas Dale

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Hascup, E.R. et al. (2013). Sub-Second Measurements of Glutamate and Other Neurotransmitter Signaling Using Enzyme-Based Ceramic Microelectrode Arrays. In: Marinesco, S., Dale, N. (eds) Microelectrode Biosensors. Neuromethods, vol 80. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-370-1_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-370-1_8

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-369-5

  • Online ISBN: 978-1-62703-370-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation