Advertisement

In Vivo Electrochemical Studies of Optogenetic Control of Glutamate Signaling Measured Using Enzyme-Based Ceramic Microelectrode Arrays

Protocol
Part of the Neuromethods book series (NM, volume 130)

Abstract

Direct electrochemical measurements of glutamate release in vivo were combined with optogenetics in order to examine light-induced control of glutamate neurotransmission in the rodent brain. Self-referenced recordings of glutamate using ceramic-based microelectrode arrays (MEAs) in hippocampus and frontal cortex demonstrated precise optical control of light-induced glutamate release through channelrhodopsin (ChR2) expression in both rat hippocampus and frontal cortex. Although the virus was only injected unilaterally, bilateral and rostro-caudal expression was observed in slice imaging, indicating diffusion and active transport of the viral particles. Methodology for the optogenetic control of glutamate signaling in the rat brain is thoroughly explained with special attention paid to MEA enzyme coating and cleaning for the benefit of other investigators. These data support that optogenetic control of glutamate signaling is robust with certain advantages as compared to other methods to modulate the in vivo control of glutamate signaling.

Key words

Glutamate Optogenetics Electrochemistry Microelectrode Array Amperometry Glutamate oxidase Neurotransmitter Biosensor 

Notes

Acknowledgments

Supported by NIDA; R21DA033796-01, DARPA; N66001-09-C-2080 and NIH; CTSA 1 UL1RR033173-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosure of competing interest: G.A.G. is principal owner of Quanteon LLC. J.E.Q., P.H., and F.P. have served as consultants to Quanteon LLC.

References

  1. 1.
    Kissinger PT, Hart JB, Adams RN (1973) Voltammetry in brain tissue—a new neurophysiological measurement. Brain Res 55(1):209–213CrossRefPubMedGoogle Scholar
  2. 2.
    McCreery RL, Dreiling R, Adams RN (1974) Voltammetry in brain tissue: the fate of injected 6-hydroxydopamine. Brain Res 73(1):15–21CrossRefPubMedGoogle Scholar
  3. 3.
    Wightman RM et al (1976) Monitoring of transmitter metabolites by voltammetry in cerebrospinal fluid following neural pathway stimulation. Nature 262(5564):145–146CrossRefPubMedGoogle Scholar
  4. 4.
    Burmeister JJ, Moxon K, Gerhardt GA (2000) Ceramic-based multisite microelectrodes for electrochemical recordings. Anal Chem 72(1):187–192CrossRefPubMedGoogle Scholar
  5. 5.
    Hu Y et al (1994) Direct measurement of glutamate release in the brain using a dual enzyme-based electrochemical sensor. Brain Res 659(1–2):117–125CrossRefPubMedGoogle Scholar
  6. 6.
    Dale N, Pearson T, Frenguelli BG (2000) Direct measurement of adenosine release during hypoxia in the CA1 region of the rat hippocampal slice. J Physiol 526(1):143–155. doi: 10.1111/j.1469-7793.2000.00143.x CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Oldenziel WH et al (2006) Evaluation of hydrogel-coated glutamate microsensors. Anal Chem 78(10):3366–3378. doi: 10.1021/ac052146s CrossRefPubMedGoogle Scholar
  8. 8.
    Zesiewicz T et al (2013) Update on treatment of essential tremor. Curr Treat Options Neurol 15(4):410–423. doi: 10.1007/s11940-013-0239-4 CrossRefPubMedGoogle Scholar
  9. 9.
    Wassum KM et al (2008) Silicon wafer-based platinum microelectrode array biosensor for near real-time measurement of glutamate in vivo. Sensors Basel Sensors 8(8):5023–5036. doi: 10.3390/s8085023 CrossRefPubMedGoogle Scholar
  10. 10.
    Lowry JP et al (1998) An amperometric glucose-oxidase/poly(o-phenylenediamine) biosensor for monitoring brain extracellular glucose: in vivo characterisation in the striatum of freely-moving rats. J Neurosci Methods 79(1):65–74CrossRefPubMedGoogle Scholar
  11. 11.
    Westerink RH (2004) Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity. Neurotoxicology 25(3):461–470. doi: 10.1016/j.neuro.2003.10.006 CrossRefPubMedGoogle Scholar
  12. 12.
    Suaud-Chagny MF et al (1993) High sensitivity measurement of brain catechols and indoles in vivo using electrochemically treated carbon-fiber electrodes. J Neurosci Methods 48(3):241–250CrossRefPubMedGoogle Scholar
  13. 13.
    Oldenziel WH et al (2006) In vivo monitoring of extracellular glutamate in the brain with a microsensor. Brain Res 1118(1):34–42. doi: 10.1016/j.brainres.2006.08.015. S0006-8993(06)02370-5 [pii]CrossRefPubMedGoogle Scholar
  14. 14.
    Tian FM et al (2009) A microelectrode biosensor for real time monitoring of L-glutamate release. Anal Chim Acta 645(1–2):86–91. doi: 10.1016/j.aca.2009.04.048 CrossRefPubMedGoogle Scholar
  15. 15.
    Rutherford EC et al (2007) Chronic second-by-second measures of L-glutamate in the central nervous system of freely moving rats. J Neurochem 102(3):712–722CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hascup KN et al (2008) Second-by-second measures of L-glutamate in the prefrontal cortex and striatum of freely moving mice. J Pharmacol Exp Ther 324(2):725–731. doi: 10.1124/jpet.107.131698 CrossRefPubMedGoogle Scholar
  17. 17.
    Stephens ML et al (2010) Real-time glutamate measurements in the putamen of awake rhesus monkeys using an enzyme-based human microelectrode array prototype. J Neurosci Methods 185(2):264–272. doi: 10.1016/j.jneumeth.2009.10.008. S0165-0270(09)00564-0 [pii]CrossRefPubMedGoogle Scholar
  18. 18.
    Hascup ER et al (2010) Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex. J Neurochem 115(6):1608–1620. doi: 10.1111/j.1471-4159.2010.07066.x CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wassum KM, Phillips PE (2015) Probing the neurochemical correlates of motivation and decision making. ACS Chem Neurosci 6(1):11–13. doi: 10.1021/cn500322y CrossRefPubMedGoogle Scholar
  20. 20.
    Phillips PE et al (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422(6932):614–618CrossRefPubMedGoogle Scholar
  21. 21.
    Park J, Takmakov P, Wightman RM (2011) In vivo comparison of norepinephrine and dopamine release in rat brain by simultaneous measurements with fast-scan cyclic voltammetry. J Neurochem 119(5):932–944. doi: 10.1111/j.1471-4159.2011.07494.x CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Gritton HJ et al (2016) Cortical cholinergic signaling controls the detection of cues. Proc Natl Acad Sci U S A 113(8):E1089–E1097. doi: 10.1073/pnas.1516134113 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Boyden ES et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268. doi: 10.1038/nn1525 CrossRefPubMedGoogle Scholar
  24. 24.
    Schweizer N et al (2014) Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion. Proc Natl Acad Sci U S A 111(21):7837–7842. doi: 10.1073/pnas.1323499111 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yau HJ et al (2016) Pontomesencephalic tegmental afferents to VTA non-dopamine neurons are necessary for appetitive Pavlovian learning. Cell Rep. doi: 10.1016/j.celrep.2016.08.007
  26. 26.
    Parrot S et al (2015) Why optogenetics needs in vivo neurochemistry. ACS Chem Neurosci 6(7):948–950. doi: 10.1021/acschemneuro.5b00003 CrossRefPubMedGoogle Scholar
  27. 27.
    Wise WS, Loh SE (1976) Equilibria and origin of minerals in system Al2O3-AlPO4-H2O. Am Mineral 61(5–6):409–413Google Scholar
  28. 28.
    Opris I et al (2011) Neural activity in frontal cortical cell layers: evidence for columnar sensorimotor processing. J Cogn Neurosci 23(6):1507–1521. doi: 10.1162/jocn.2010.21534 CrossRefPubMedGoogle Scholar
  29. 29.
    Burmeister J et al (2002) Improved ceramic-based multisite microelectrode for rapid measurements of L-glutamate in the CNS. J Neurosci Methods 119(2):163–171CrossRefPubMedGoogle Scholar
  30. 30.
    Burmeister JJ et al (2013) Glutaraldehyde cross-linked glutamate oxidase coated microelectrode arrays: selectivity and resting levels of glutamate in the CNS. ACS Chem Neurosci 4(5):721–728. doi: 10.1021/cn4000555 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Hascup KN et al (2011) Resting glutamate levels and rapid glutamate transients in the prefrontal cortex of the flinders sensitive line rat: a genetic rodent model of depression. Neuropsychopharmacology 36(8):1769–1777. doi: 10.1038/npp.2011.60. npp201160 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ulusoy A et al (2009) Dose optimization for long-term rAAV-mediated RNA interference in the nigrostriatal projection neurons. Mol Ther 17(9):1574–1584. doi: 10.1038/mt.2009.142 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    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(5):1037–1042CrossRefPubMedGoogle Scholar
  34. 34.
    Kusakabe H et al (1983) Purification and properties of a new enzyme, L-glutamate oxidase, from streptomyces SP X-199-6 grown on wheat bran. Agric Biol Chem 47(6):1323–1328Google Scholar
  35. 35.
    Hinzman JM et al (2010) Diffuse brain injury elevates tonic glutamate levels and potassium-evoked glutamate release in discrete brain regions at two days post-injury: an enzyme-based microelectrode array study. J Neurotrauma 27(5):889–899. doi: 10.1089/neu.2009.1238 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Stephens ML et al (2009) Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2009.05.009. S0197-4580(09)00172-9 [pii]
  37. 37.
    Day BK et al (2006) Microelectrode array studies of basal and potassium-evoked release of L-glutamate in the anesthetized rat brain. J Neurochem 96(6):1626–1635CrossRefPubMedGoogle Scholar
  38. 38.
    Hinzman JM et al (2012) Disruptions in the regulation of extracellular glutamate by neurons and glia in the rat striatum two days after diffuse brain injury. J Neurotrauma 29(6):1197–1208. doi: 10.1089/neu.2011.2261 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dash MB et al (2009) Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states. J Neurosci 29(3):620–629. doi: 10.1523/JNEUROSCI.5486-08.2009. 29/3/620 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hampson RE et al (2012) Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing. J Neural Eng 9(5):056012. doi: 10.1088/1741-2560/9/5/056012 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Opris I et al (2012) Closing the loop in primate prefrontal cortex: inter-laminar processing. Front Neural Circuits 6:88. doi: 10.3389/fncir.2012.00088 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Opris I et al (2012) Columnar processing in primate pFC: evidence for executive control microcircuits. J Cogn Neurosci. doi: 10.1162/jocn_a_00307
  43. 43.
    Onifer SM, Quintero JE, Gerhardt GA (2012) Cutaneous and electrically evoked glutamate signaling in the adult rat somatosensory system. J Neurosci Methods 208(2):146–154. doi: 10.1016/j.jneumeth.2012.05.013 CrossRefPubMedGoogle Scholar
  44. 44.
    Zhang H, Lin SC, Nicolelis MA (2009) Acquiring local field potential information from amperometric neurochemical recordings. J Neurosci Methods 179(2):191–200. doi: 10.1016/j.jneumeth.2009.01.023. S0165-0270(09)00052-1 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Quintero JE et al (2007) Amperometric measures of age-related changes in glutamate regulation in the cortex of rhesus monkeys. Exp Neurol 208(2):238–246CrossRefPubMedGoogle Scholar
  46. 46.
    Howe WM et al (2013) Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans. J Neurosci 33(20):8742–8752. doi: 10.1523/jneurosci.5809-12.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Konradsson-Geuken A et al (2010) Cortical kynurenic acid bi-directionally modulates prefrontal glutamate levels as assessed by microdialysis and rapid electrochemistry. Neuroscience 169(4):1848–1859. doi: 10.1016/j.neuroscience.2010.05.052. S0306-4522(10)00792-X [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Zhou N et al (2013) Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression. J Cereb Blood Flow Metab 33(10):1582–1594. doi: 10.1038/jcbfm.2013.113 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Choi Hyun B et al (2012) Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase. Neuron 75(6):1094–1104. doi: 10.1016/j.neuron.2012.08.032 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Zhang F et al (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5(3):439–456. doi: 10.1038/nprot.2009.226 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Yizhar O et al (2011) Optogenetics in neural systems. Neuron 71(1):9–34. doi: 10.1016/j.neuron.2011.06.004 CrossRefPubMedGoogle Scholar
  52. 52.
    Bernstein JG et al (2008) Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons. Proc SPIE Int Soc Opt Eng 6854:68540h. doi: 10.1117/12.768798 PubMedPubMedCentralGoogle Scholar
  53. 53.
    Miller EM et al (2015) Simultaneous glutamate recordings in the frontal cortex network with multisite biomorphic microelectrodes: new tools for ADHD research. J Neurosci Methods. doi: 10.1016/j.jneumeth.2015.01.018
  54. 54.
    Stephens ML et al (2014) Tonic glutamate in CA1 of aging rats correlates with phasic glutamate dysregulation during seizure. Epilepsia 55(11):1817–1825. doi: 10.1111/epi.12797 CrossRefPubMedGoogle Scholar
  55. 55.
    Hunsberger HC et al (2015) P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway. J Neurochem 132(2):169–182. doi: 10.1111/jnc.12967 CrossRefPubMedGoogle Scholar
  56. 56.
    Thomas TC et al (2012) Hypersensitive glutamate signaling correlates with the development of late-onset behavioral morbidity in diffuse brain-injured circuitry. J Neurotrauma 29(2):187–200. doi: 10.1089/neu.2011.2091 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Hinzman JM et al (2015) Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions. Exp Neurol 267:243–253. doi: 10.1016/j.expneurol.2015.03.014 CrossRefPubMedGoogle Scholar
  58. 58.
    Quintero JE et al (2011) Methodology for rapid measures of glutamate release in rat brain slices using ceramic-based microelectrode arrays: basic characterization and drug pharmacology. Brain Res 1401:1–9. doi: 10.1016/j.brainres.2011.05.025 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Department of Anatomy and NeurobiologyUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Lund UniversityLundSweden

Personalised recommendations