Abstract
Functional multineuron calcium imaging (fMCI) is a large-scale technique used to access brain function on a single-neuron scale. It detects the activity of individual neurons by imaging action potential-evoked transient calcium influxes into their cell bodies. fMCI has recently been used as a high-throughput research tool to examine how neuronal activity is altered in animal models of brain diseases, for example stroke, Alzheimer’s disease, and epilepsy, and to estimate how pharmacological agents act on normal and abnormal states of neuronal networks. It offers unique opportunities to discover the mechanisms underlying neurological disorders and new therapeutic targets.
Similar content being viewed by others
References
Shoham D, Glaser DE, Arieli A, Kenet T, Wijnbergen C, Toledo Y, Hildesheim R, Grinvald A (1999) Neuron 24:791–802
Raichle ME (1998) Proc Natl Acad Sci USA 95:765–772
Orbach HS, Cohen LB, Grinvald A (1985) J Neurosci 5:1886–1895
Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN (1986) Nature 324:361–364
Logothetis N, Merkle H, Augath M, Trinath T, Ugurbil K (2002) Neuron 35:227–242
Sasaki T, Matsuki N, Ikegaya Y (2007) J Neurosci 27:517–528
Sasaki T, Takahashi N, Matsuki N, Ikegaya Y (2008) J Neurophysiol 100:1668–1676
Nimmerjahn A, Kirchhoff F, Kerr JN, Helmchen F (2004) Nat Methods 1:31–37
Yuste R, Katz LC (1991) Neuron 6:333–344
Miyawaki A (2005) Neuron 48:189–199
Tian L, Hires SA, Mao T, Huber D, Chiappe ME, Chalasani SH, Petreanu L, Akerboom J, McKinney SA, Schreiter ER, Bargmann CI, Jayaraman V, Svoboda K, Looger LL (2009) Nat Methods 6:875–881
Dreosti E, Odermatt B, Dorostkar MM, Lagnado L (2009) Nat Methods 6:883–889
Mank M, Santos AF, Direnberger S, Mrsic-Flogel TD, Hofer SB, Stein V, Hendel T, Reiff DF, Levelt C, Borst A, Bonhoeffer T, Hübener M, Griesbeck O (2008) Nat Methods 5:805–811
Bonifazi P, Goldin M, Picardo MA, Jorquera I, Cattani A, Bianconi G, Represa A, Ben Ari Y, Cossart R (2009) Science 326:1419–1424
Namiki S, Matsuki N, Ikegaya Y (2009) Nat Proceedings 2009.2893.1
Buzsaki G (2004) Nat Neurosci 7:446–451
Cossart R, Aronov D, Yuste R (2003) Nature 423:283–288
Ikegaya Y, Aaron G, Cossart R, Aronov D, Lampl I, Ferster D, Yuste R (2004) Science 304:559–564
MacLean JN, Watson BO, Aaron GB, Yuste R (2005) Neuron 48:811–823
Denk W, Strickler JH, Webb WW (1990) Science 248:73–76
Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) Proc Natl Acad Sci USA 100:7319–7324
Ohki K, Chung S, Ch'ng YH, Kara P, Reid RC (2005) Nature 433:597–603
Ohki K, Chung S, Kara P, Hubener M, Bonhoeffer T, Reid RC (2006) Nature 442:925–928
Nagayama S, Zeng S, Xiong W, Fletcher ML, Masurkar AV, Davis DJ, Pieribone VA, Chen WR (2007) Neuron 53:789–803
Kerr JN, de Kock CP, Greenberg DS, Bruno RM, Sakmann B, Helmchen F (2007) J Neurosci 27:13316–13328
Helmchen F, Fee MS, Tank DW, Denk W (2001) Neuron 31:903–912
Engelbrecht CJ, Johnston RS, Seibel EJ, Helmchen F (2008) Opt Exp 16:5556–5564
Dombeck DA, Khabbaz AN, Collman F, Adelman TL, Tank DW (2007) Neuron 56:43–57
Harvey CD, Collman F, Dombeck DA, Tank DW (2009) Nature 461:941–946
Kerr JN, Greenberg D, Helmchen F (2005) Proc Natl Acad Sci USA 102:14063–14068
Ramdya P, Reiter B, Engert F (2006) J Neurosci Methods 157:230–237
Greenberg DS, Houweling AR, Kerr JN (2008) Nat Neurosci 11:749–751
Yaksi E, Friedrich RW (2006) Nat Methods 3:377–383
Peterlin ZA, Kozloski J, Mao BQ, Tsiola A, Yuste R (2000) Proc Natl Acad Sci USA 97:3619–3624
Aaron G, Yuste R (2006) Synapse 60:437–440
Sasaki T, Minamisawa G, Takahashi N, Matsuki N, Ikegaya Y (2009) J Neurophysiol 102:636–643
Nikolenko V, Poskanzer KE, Yuste R (2007) Nat Methods 4:943–950
Mizunuma M, Takahashi N, Usami A, Matsuki N, Ikegaya Y (2009) J Pharmacol Sci 110:117–121
Tauskela JS, Fang H, Hewitt M, Brunette E, Ahuja T, Thivierge JP, Comas T, Mealing GA (2008) J Biol Chem 283:34667–34676
Winship IR, Murphy TH (2008) J Neurosci 28:6592–6606
Gotz J, Ittner LM (2008) Nat Rev Neurosci 9:532–544
Eichhoff G, Busche MA, Garaschuk O (2008) Eur J Nucl Med Mol Imaging 35(Suppl 1):S99–S106
Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O (2008) Science 321:1686–1689
Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ (2009) Science 323:1211–1215
Badea T, Goldberg J, Mao B, Yuste R (2001) J Neurobiol 48:215–227
Sasaki T, Kimura K, Tsukamoto M, Matsuki N, Ikegaya Y (2006) J Physiol 574:195–208
Trevelyan AJ, Sussillo D, Yuste R (2007) J Neurosci 27:3383–3387
Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J, Oberheim N, Lou N, Wang X, Zielke HR, Kang J, Nedergaard M (2005) Nat Med 11:973–981
Usami A, Sasaki T, Satoh N, Akiba T, Yokoshima S, Fukuyama T, Yamatsugu K, Kanai M, Shibasaki M, Matsuki N, Ikegaya Y (2008) J Pharmacol Sci 106:659–662
Helmchen F, Denk W (2005) Nat Methods 2:932–940
Kuga N, Hirata T, Sakai I, Tanikawa Y, Chiou HY, Kitanishi T, Matsuki N, Ikegaya Y (2009) J Physiol 587:745–752
Levene MJ, Dombeck DA, Kasischke KA, Molloy RP, Webb WW (2004) J Neurophysiol 91:1908–1912
Barretto RP, Messerschmidt B, Schnitzer MJ (2009) Nat Methods 6:511–512
Ikegaya Y, Le Bon-Jego M, Yuste R (2005) Neurosci Res 52:132–138
Takahashi N, Sasaki T, Usami A, Matsuki N, Ikegaya Y (2007) Neurosci Res 58:219–225
Nevian T, Helmchen F (2007) Pflugers Arch 454:675–688
Crepel V, Aronov D, Jorquera I, Represa A, Ben-Ari Y, Cossart R (2007) Neuron 54:105–120
Ozden I, Lee HM, Sullivan MR, Wang SS-H (2008) J Neurophysiol 100:495–503
Mukamel EA, Nimmerjahn A, Schnitzer MJ (2009) Neuron 63:747–760
Author information
Authors and Affiliations
Corresponding author
Appendices
Appendix
Publication list of methods and tools for details
Loading procedure for calcium indicators
In vitro fMCI
(Bath application) Ikegaya et al, 2005 [54]; Takahashi et al., 2007 [55]
(Pressure injection) Stosiek et al., 2003 [21]
In vivo fMCI
(Pressure injection) Stosiek et al., 2003 [21]; Nimmejahn et al., 2004 [8]; Ohki et al, 2005 [22]
(Electroporation) Nevian and Helmchem, 2007 [56]; Nagayama et al., 2007 [24]
fMCI data analysis
Cell identification
(Fluorescence contour) Crepel et al., 2007 [57]
(Correlation based) Ozden et al. 2008 [58]
(Spatio-temporal independent component analysis) Mukamel et al., 2009 [59]
Extraction of calcium signals (spike detection)
(Temporal deconvolution) Yaksi and Friedrich, 2006 [33]
(Template matching) Kerr et al., 2005 [30]; Greenberg et al., 2008 [32]
(Machine learning) Sasaki et al., 2008 [7]
(Spatio-temporal independent component analysis) Mukamel et al., 2009 [59]
Rights and permissions
About this article
Cite this article
Takahashi, N., Takahara, Y., Ishikawa, D. et al. Functional multineuron calcium imaging for systems pharmacology. Anal Bioanal Chem 398, 211–218 (2010). https://doi.org/10.1007/s00216-010-3740-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-010-3740-6