Advertisement

Imaging Glutamate with Genetically Encoded Fluorescent Sensors

  • Gerard J. BroussardEmail author
  • Elizabeth K. Unger
  • Ruqiang Liang
  • Brian P. McGrew
  • Lin TianEmail author
Protocol
  • 930 Downloads
Part of the Neuromethods book series (NM, volume 130)

Abstract

Superimposed on the vast and complex synaptic network is a largely invisible set of chemical inputs, such as neurotransmitters and neuromodulators, that exert a profound influence on brain function across many structures and temporal scales. Thus, the determination of the spatiotemporal relationships between these chemical signals with synaptic resolution in the intact brain is essential to decipher the codes for transferring information across circuitry and systems. Recent advances in imaging technology have been employed to determine the extent of spatial and temporal neurotransmitter dynamics in the brain, especially glutamate, the most abundant excitatory neurotransmitter. Here, we discuss recent imaging approaches, particularly with a focus on the design and application of genetically encoded indicator iGluSnFR, in analyzing glutamate transients in vitro, ex vivo, and in vivo.

Key words

Glutamate iGluSnFR Fluorescent sensor Genetically encoded indicators of neural activity Protein engineering Fluorescent functional imaging 

Notes

Acknowledgements

This work is supported by NIH DP2 MH107059 (L.T.), Brain Initiative U01NS090604 (L.T., E.K.U., G.J.B.) and U01NS09058 (R.L.), Rita Allen Foundation (R.L.), Human Frontier Research Program (G.J.B.), and NIH R21NS095325 (B.P.M.). We are grateful for the contributions of Douglas Unger in generating the rotation matrix. We are grateful to Loren Looger, Jonathan Marvin and Philip Borden for their pioneering work in engineering iGluSnFR and critical comments. We also thank Lisa Makhoul for careful reading and discussion of this book chapter.

References

  1. 1.
    Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145. doi: 10.1097/00004647-200110000-00001 CrossRefPubMedGoogle Scholar
  2. 2.
    Kwon H-B, Sabatini BL (2011) Glutamate induces de novo growth of functional spines in developing cortex. Nature 474:100–104. doi: 10.1038/nature09986 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lüscher C, Malenka RC (2012) NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a005710
  4. 4.
    Volterra A, Liaudet N, Savtchouk I (2014) Astrocyte Ca2+ signalling: an unexpected complexity. Nat Rev Neurosci 15:327–335. doi: 10.1038/nrn3725 CrossRefPubMedGoogle Scholar
  5. 5.
    Arundine M, Tymianski M (2004) Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 61:657–668. doi: 10.1007/s00018-003-3319-x CrossRefPubMedGoogle Scholar
  6. 6.
    Woodroofe N, Amor S (2014) Neuroinflammation and CNS disorders. John Wiley & Sons, West Sussex, UKCrossRefGoogle Scholar
  7. 7.
    Clements JD (1996) Transmitter timecourse in the synaptic cleft: its role in central synaptic function. Trends Neurosci 19:163–171. doi: 10.1016/S0166-2236(96)10024-2 CrossRefPubMedGoogle Scholar
  8. 8.
    Marcaggi P, Attwell D (2004) Role of glial amino acid transporters in synaptic transmission and brain energetics. Glia 47:217–225. doi: 10.1002/glia.20027 CrossRefPubMedGoogle Scholar
  9. 9.
    Ventura R, Harris KM (1999) Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci 19:6897–6906PubMedGoogle Scholar
  10. 10.
    Veruki ML, Mørkve SH, Hartveit E (2006) Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nat Neurosci 9:1388–1396. doi: 10.1038/nn1793 CrossRefPubMedGoogle Scholar
  11. 11.
    Moussawi K, Riegel A, Nair S, Kalivas PW (2011) Extracellular glutamate: functional compartments operate in different concentration ranges. Front Syst Neurosci. doi: 10.3389/fnsys.2011.00094
  12. 12.
    Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326:483–504. doi: 10.1007/s00441-006-0266-5 CrossRefPubMedGoogle Scholar
  13. 13.
    Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108. doi: 10.1146/annurev.ne.17.030194.000335 CrossRefPubMedGoogle Scholar
  14. 14.
    Zito K, Scheuss V (2009) NMDA receptor function and physiological modulation. Encyclopedia Neurosci. doi: 10.1016/b978-008045046-9.01225-0
  15. 15.
    Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237. doi: 10.1146/annurev.pharmtox.37.1.205 CrossRefPubMedGoogle Scholar
  16. 16.
    Marcaggi P, Mutoh H, Dimitrov D et al (2009) Optical measurement of mGluR1 conformational changes reveals fast activation, slow deactivation, and sensitization. Proc Natl Acad Sci U S A 106:11388–11393. doi: 10.1073/pnas.0901290106 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vafabakhsh R, Levitz J, Isacoff EY (2015) Conformational dynamics of a class C G-protein-coupled receptor. Nature 524:497–501. doi: 10.1038/nature14679 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Masugi-Tokita M, Shigemoto R (2007) High-resolution quantitative visualization of glutamate and GABA receptors at central synapses. Curr Opin Neurobiol 17:387–393. doi: 10.1016/j.conb.2007.04.012 CrossRefPubMedGoogle Scholar
  19. 19.
    Araque A, Carmignoto G, Haydon PG (2001) Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63:795–813. doi: 10.1146/annurev.physiol.63.1.795 CrossRefPubMedGoogle Scholar
  20. 20.
    Chefer VI, Thompson AC, Zapata A, Shippenberg TS (2009) Overview of brain microdialysis. Curr Protoc Neurosci. Chapter 7:Unit7.1. doi:  10.1002/0471142301.ns0701s47
  21. 21.
    McLamore ES, Mohanty S, Shi J et al (2010) A self-referencing glutamate biosensor for measuring real time neuronal glutamate flux. J Neurosci Methods 189:14–22. doi: 10.1016/j.jneumeth.2010.03.001 CrossRefPubMedGoogle Scholar
  22. 22.
    Namiki S, Sakamoto H, Iinuma S et al (2007) Optical glutamate sensor for spatiotemporal analysis of synaptic transmission. Eur J Neurosci 25:2249–2259. doi: 10.1111/j.1460-9568.2007.05511.x CrossRefPubMedGoogle Scholar
  23. 23.
    Brun MA, Tan K-T, Griss R et al (2012) A semisynthetic fluorescent sensor protein for glutamate. J Am Chem Soc 134:7676–7678. doi: 10.1021/ja3002277 CrossRefPubMedGoogle Scholar
  24. 24.
    Takikawa K, Asanuma D, Namiki S et al (2014) High-throughput development of a hybrid-type fluorescent glutamate sensor for analysis of synaptic transmission. Angew Chem Int Ed 53:13439–13443. doi: 10.1002/anie.201407181 CrossRefGoogle Scholar
  25. 25.
    Oldenziel WH, Beukema W, Westerink BHC (2004) Improving the reproducibility of hydrogel-coated glutamate microsensors by using an automated dipcoater. J Neurosci Methods 140:117–126. doi: 10.1016/j.jneumeth.2004.04.038 CrossRefPubMedGoogle Scholar
  26. 26.
    Rahman MA, Kwon N-H, Won M-S et al (2005) Functionalized conducting polymer as an enzyme-immobilizing substrate: an amperometric glutamate microbiosensor for in vivo measurements. Anal Chem 77:4854–4860. doi: 10.1021/ac050558v CrossRefPubMedGoogle Scholar
  27. 27.
    Hu Y, Mitchell KM, Albahadily FN et al (1994) Direct measurement of glutamate release in the brain using a dual enzyme-based electrochemical sensor. Brain Res 659:117–125CrossRefPubMedGoogle Scholar
  28. 28.
    Broussard GJ, Liang R, Tian L (2014) Monitoring activity in neural circuits with genetically encoded indicators. Front Mol Neurosci. doi: 10.3389/fnmol.2014.00097
  29. 29.
    Lin MZ, Schnitzer MJ (2016) Genetically encoded indicators of neuronal activity. Nat Neurosci 19:1142–1153. doi: 10.1038/nn.4359 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nakai J, Ohkura M, Imoto K (2001) A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nat Biotechnol 19:137–141. doi: 10.1038/84397 CrossRefPubMedGoogle Scholar
  31. 31.
    Tallini YN, Ohkura M, Choi B-R et al (2006) Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca2+ indicator GCaMP2. Proc Natl Acad Sci U S A 103:4753–4758. doi: 10.1073/pnas.0509378103 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Tian L, Hires SA, Mao T et al (2009) Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat Methods 6:875–881. doi: 10.1038/nmeth.1398 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Akerboom J, Chen T-W, Wardill TJ et al (2012) Optimization of a GCaMP calcium indicator for neural activity imaging. J Neurosci 32:13819–13840. doi: 10.1523/JNEUROSCI.2601-12.2012 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Chen T-W, Wardill TJ, Sun Y et al (2013) Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499:295–300. doi: 10.1038/nature12354 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Baird GS, Zacharias DA, Tsien RY (1999) Circular permutation and receptor insertion within green fluorescent proteins. Proc Natl Acad Sci U S A 96:11241–11246. doi: 10.1073/pnas.96.20.11241 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wang Q, Shui B, Kotlikoff MI, Sondermann H (2008) Structural basis for calcium sensing by GCaMP2. Structure 16:1817–1827. doi: 10.1016/j.str.2008.10.008 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Petreanu L, Gutnisky DA, Huber D et al (2012) Activity in motor-sensory projections reveals distributed coding in somatosensation. Nature 489:299–303. doi: 10.1038/nature11321 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Shigetomi E, Bushong EA, Haustein MD et al (2013) Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses. J Gen Physiol 141:633–647. doi: 10.1085/jgp.201210949 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Issa JB, Haeffele BD, Agarwal A et al (2014) Multiscale optical Ca2+ imaging of tonal organization in mouse auditory cortex. Neuron 83:944–959. doi: 10.1016/j.neuron.2014.07.009 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Vanni MP, Murphy TH (2014) Mesoscale transcranial spontaneous activity mapping in GCaMP3 transgenic mice reveals extensive reciprocal connections between areas of somatomotor cortex. J Neurosci 34:15931–15946. doi: 10.1523/JNEUROSCI.1818-14.2014 CrossRefPubMedGoogle Scholar
  41. 41.
    Murakami T, Yoshida T, Matsui T, Ohki K (2015) Wide-field Ca2+ imaging reveals visually evoked activity in the retrosplenial area. Front Mol Neurosci. doi: 10.3389/fnmol.2015.00020
  42. 42.
    Sun XR, Badura A, Pacheco DA et al (2013) Fast GCaMPs for improved tracking of neuronal activity. Nat Commun 4:2170. doi: 10.1038/ncomms3170 PubMedGoogle Scholar
  43. 43.
    Helassa N, Zhang X, Conte I et al (2015) Fast-response calmodulin-based fluorescent indicators reveal rapid intracellular calcium dynamics. Sci Rep 5:15978. doi: 10.1038/srep15978 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Huber D, Gutnisky DA, Peron S et al (2012) Multiple dynamic representations in the motor cortex during sensorimotor learning. Nature 484:473–478. doi: 10.1038/nature11039 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ziv Y, Burns LD, Cocker ED et al (2013) Long-term dynamics of CA1 hippocampal place codes. Nat Neurosci 16:264–266. doi: 10.1038/nn.3329 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Vogt N (2015) Voltage sensors: challenging, but with potential. Nat Methods 12:921–924. doi: 10.1038/nmeth.3591 CrossRefPubMedGoogle Scholar
  47. 47.
    Fioravante D, Regehr WG (2011) Short-term forms of presynaptic plasticity. Curr Opin Neurobiol 21:269–274. doi: 10.1016/j.conb.2011.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Xie Y, Chan AW, McGirr A et al (2016) Resolution of high-frequency mesoscale intracortical maps using the genetically encoded glutamate sensor iGluSnFR. J Neurosci 36:1261–1272. doi: 10.1523/JNEUROSCI.2744-15.2016 CrossRefPubMedGoogle Scholar
  49. 49.
    Vyleta NP, Smith SM (2011) Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor. J Neurosci 31:4593–4606. doi: 10.1523/JNEUROSCI.6398-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Schellenberg GD, Furlong CE (1977) Resolution of the multiplicity of the glutamate and aspartate transport systems of Escherichia coli. J Biol Chem 252:9055–9064PubMedGoogle Scholar
  51. 51.
    Dwyer MA, Hellinga HW (2004) Periplasmic binding proteins: a versatile superfamily for protein engineering. Curr Opin Struct Biol 14:495–504. doi: 10.1016/j.sbi.2004.07.004 CrossRefPubMedGoogle Scholar
  52. 52.
    Okumoto S, Looger LL, Micheva KD et al (2005) Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors. Proc Natl Acad Sci U S A 102:8740–8745. doi: 10.1073/pnas.0503274102 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Hires SA, Zhu Y, Tsien RY (2008) Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proc Natl Acad Sci U S A 105:4411–4416. doi: 10.1073/pnas.0712008105 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Marvin JS, Borghuis BG, Tian L et al (2013) An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat Methods 10:162–170. doi: 10.1038/nmeth.2333 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Marvin JS, Schreiter ER, Echevarría IM, Looger LL (2011) A genetically encoded, high-signal-to-noise maltose sensor. Proteins 79:3025–3036. doi: 10.1002/prot.23118 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Brunert D, Tsuno Y, Rothermel M et al (2016) Cell-type-specific modulation of sensory responses in olfactory bulb circuits by serotonergic projections from the raphe nuclei. J Neurosci 36:6820–6835. doi: 10.1523/JNEUROSCI.3667-15.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Borghuis BG, Marvin JS, Looger LL, Demb JB (2013) Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. J Neurosci 33:10972–10985. doi: 10.1523/JNEUROSCI.1241-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Borghuis BG, Looger LL, Tomita S, Demb JB (2014) Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina. J Neurosci 34:6128–6139. doi: 10.1523/JNEUROSCI.4941-13.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Yonehara K, Farrow K, Ghanem A et al (2013) The first stage of cardinal direction selectivity is localized to the dendrites of retinal ganglion cells. Neuron 79:1078–1085. doi: 10.1016/j.neuron.2013.08.005 CrossRefPubMedGoogle Scholar
  60. 60.
    Baxter PS, Bell KFS, Hasel P et al (2015) Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system. Nat Commun 6:6761. doi: 10.1038/ncomms7761 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    O’Herron P, Chhatbar PY, Levy M et al (2016) Neural correlates of single-vessel haemodynamic responses in vivo. Nature. doi: 10.1038/nature17965
  62. 62.
    Bao H, Goldschen-Ohm M, Jeggle P et al (2016) Exocytotic fusion pores are composed of both lipids and proteins. Nat Struct Mol Biol 23:67–73. doi: 10.1038/nsmb.3141 CrossRefPubMedGoogle Scholar
  63. 63.
    Poleg-Polsky A, Diamond JS (2016) Retinal circuitry balances contrast tuning of excitation and inhibition to enable reliable computation of direction selectivity. J Neurosci 36:5861–5876. doi: 10.1523/JNEUROSCI.4013-15.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Zhang R, Li X, Kawakami K, Du J (2016) Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors. Nat Commun 7:12650. doi: 10.1038/ncomms12650 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Haustein MD, Kracun S, X-H L et al (2014) Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway. Neuron 82:413–429. doi: 10.1016/j.neuron.2014.02.041 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Rosa JM, Bos R, Sack GS et al (2015) Neuron-glia signaling in developing retina mediated by neurotransmitter spillover. eLife 4:e09590. doi: 10.7554/eLife.09590 CrossRefPubMedCentralGoogle Scholar
  67. 67.
    Stork T, Sheehan A, Tasdemir-Yilmaz OE, Freeman MR (2014) Neuron-glia interactions through the heartless FGF receptor signaling pathway mediate morphogenesis of drosophila astrocytes. Neuron 83:388–403. doi: 10.1016/j.neuron.2014.06.026 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Parsons MP, Vanni MP, Woodard CL et al (2016) Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models. Nat Commun 7:11251. doi: 10.1038/ncomms11251 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Poskanzer KE, Yuste R (2016) Astrocytes regulate cortical state switching in vivo. Proc Natl Acad Sci U S A 113:E2675–E2684. doi: 10.1073/pnas.1520759113 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Looger LL, Griesbeck O (2012) Genetically encoded neural activity indicators. Curr Opin Neurobiol 22:18–23. doi: 10.1016/j.conb.2011.10.024 CrossRefPubMedGoogle Scholar
  71. 71.
    Akerboom J, Tian L, Marvin J, Looger L (2012) Engineering and application of genetically encoded calcium indicators. In: Martin J-R (ed) Genetically encoded functional indicators. Humana Press, New York, pp 125–147CrossRefGoogle Scholar
  72. 72.
    Moretti R, Bender BJ, Allison B, Meiler J (2016) Rosetta and the design of ligand binding sites. Methods Mol Biol 1414:47–62. doi: 10.1007/978-1-4939-3569-7_4 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. doi: 10.1002/jcc.20084 CrossRefPubMedGoogle Scholar
  74. 74.
    Bender BJ, Cisneros A, Duran AM et al (2016) Protocols for molecular modeling with Rosetta3 and RosettaScripts. Biochemistry 55:4748–4763. doi: 10.1021/acs.biochem.6b00444 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Hughes MD, Nagel DA, Santos AF et al (2003) Removing the redundancy from randomised gene libraries. J Mol Biol 331:973–979CrossRefPubMedGoogle Scholar
  76. 76.
    Edelheit O, Hanukoglu A, Hanukoglu I (2009) Simple and efficient site-directed mutagenesis using two single-primer reactions in parallel to generate mutants for protein structure-function studies. BMC Biotechnol 9:61. doi: 10.1186/1472-6750-9-61 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Liu H, Naismith JH (2008) An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol. BMC Biotechnol 8:91. doi: 10.1186/1472-6750-8-91 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Quan J, Tian J (2011) Circular polymerase extension cloning for high-throughput cloning of complex and combinatorial DNA libraries. Nat Protoc 6:242–251. doi: 10.1038/nprot.2010.181 CrossRefPubMedGoogle Scholar
  79. 79.
    Kunkel TA (1985) Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A 82:488–492CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Huang R, Fang P, Kay BK (2012) Improvements to the Kunkel mutagenesis protocol for constructing primary and secondary phage-display libraries. Methods 58:10–17. doi: 10.1016/j.ymeth.2012.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Cadwell RC, Joyce GF (1992) Randomization of genes by PCR mutagenesis. Genome Res 2:28–33. doi: 10.1101/gr.2.1.28 CrossRefGoogle Scholar
  82. 82.
    Gruet A, Longhi S, Bignon C (2012) One-step generation of error-prone PCR libraries using Gateway® technology. Microb Cell Factories 11:14. doi: 10.1186/1475-2859-11-14 CrossRefGoogle Scholar
  83. 83.
    Drobizhev M, Makarov NS, Tillo SE et al (2011) Two-photon absorption properties of fluorescent proteins. Nat Methods 8:393–399. doi: 10.1038/nmeth.1596 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Makarov NS, Drobizhev M, Rebane A (2008) Two-photon absorption standards in the 550–1600 nm excitation wavelength range. Opt Express 16:4029–4047. doi: 10.1364/OE.16.004029 CrossRefPubMedGoogle Scholar
  85. 85.
    Vandenberghe LH, Xiao R, Lock M et al (2010) Efficient serotype-dependent release of functional vector into the culture medium during adeno-associated virus manufacturing. Hum Gene Ther 21:1251–1257. doi: 10.1089/hum.2010.107 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Paxinos G, Franklin KBJ (2012) Paxinos and Franklin’s the mouse brain in stereotaxic coordinates, 4th edn. Academic Press, AmsterdamGoogle Scholar
  87. 87.
    Deverman BE, Pravdo PL, Simpson BP et al (2016) Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat Biotechnol 34:204–209. doi: 10.1038/nbt.3440 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Chia TH, Levene MJ (2009) Microprisms for in vivo multilayer cortical imaging. J Neurophysiol 102:1310–1314. doi: 10.1152/jn.91208.2008 CrossRefPubMedGoogle Scholar
  89. 89.
    Low RJ, Gu Y, Tank DW (2014) Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex. Proc Natl Acad Sci U S A 111:18739–18744. doi: 10.1073/pnas.1421753111 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Guo ZV, Hires SA, Li N, O'Connor DH, Komiyama T, Ophir E, Huber D, Bonardi C, Morandell K, Gutnisky D, Peron S, Xu N-l, Cox J, Svoboda K (2014) Procedures for behavioral experiments in head-fixed mice. PLoS One 9(2). doi: 10.1371/journal.pone.0088678
  91. 91.
    Kislin M, Mugantseva E, Molotkov D, Kulesskaya N, Khirug S, Kirilkin I, Pryazhnikov E, Kolikova J, Toptunov D, Yuryev M, Giniatullin R, Voikar V, Rivera C, Rauvala H, Khiroug L (2014) Flat-floored air-lifted platform: a new method for combining behavior with microscopy or electrophysiology on awake freely moving rodents. J Vis Exp 88:–e51869. doi: 10.3791/51869
  92. 92.
    Urbain N, Gervasoni D, Soulière F et al (2000) Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat. Eur J Neurosci 12:3361–3374CrossRefPubMedGoogle Scholar
  93. 93.
    Urbain N, Salin PA, Libourel P-A et al (2015) Whisking-related changes in neuronal firing and membrane potential dynamics in the somatosensory thalamus of awake mice. Cell Rep 13:647–656. doi: 10.1016/j.celrep.2015.09.029 CrossRefPubMedGoogle Scholar
  94. 94.
    Guizar-Sicairos M, Thurman ST, Fienup JR (2008) Efficient subpixel image registration algorithms. Opt Lett 33(2):156–158CrossRefPubMedGoogle Scholar
  95. 95.
    Wu M, Chen R, Soh J, Shen Y, Jiao L, Wu J, Chen X, Ji R, Hong M (2016) Super-focusing of center-covered engineered microsphere. Sci Rep 6:31637. doi: 10.1038/srep31637 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Granseth B, Odermatt B, Royle SJ, Lagnado L (2006) Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at hippocampal synapses. Neuron 51:773–786. doi: 10.1016/j.neuron.2006.08.029 CrossRefPubMedGoogle Scholar
  97. 97.
    Shen Y, Lai T, Campbell RE (2015) Red fluorescent proteins (RFPs) and RFP-based biosensors for neuronal imaging applications. Neurophotonics 2:031203. doi: 10.1117/1.NPh.2.3.031203 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dana H, Mohar B, Sun Y et al (2016) Sensitive red protein calcium indicators for imaging neural activity. Elife. doi: 10.7554/eLife.12727
  99. 99.
    Lin JY, Knutsen PM, Muller A et al (2013) ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci 16:1499–1508. doi: 10.1038/nn.3502 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Drobizhev M, Tillo S, Makarov NS, Hughes TE, Rebane A (2009) Absolute two-photon absorption spectra and two-photon brightness of orange and red fluorescent proteins. J Phys Chem B 113(4):855–859. doi: 10.1021/jp8087379 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular MedicineUniversity of California DavisDavisUSA
  2. 2.Neuroscience Graduate GroupUniversity of California DavisDavisUSA

Personalised recommendations