Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation fMRI

  • Laura Pérez-Cervera
  • José María Caramés
  • Luis Miguel Fernández-Mollá
  • Andrea Moreno
  • Begoña Fernández
  • Elena Pérez-Montoyo
  • David Moratal
  • Santiago Canals
  • Jesús Pacheco-Torres
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1718)

Abstract

Since its discovery in the early 90s, BOLD signal-based functional Magnetic Resonance Imaging (fMRI) has become a fundamental technique for the study of brain activity in basic and clinical research. Functional MRI signals provide an indirect but robust and quantitative readout of brain activity through the tight coupling between cerebral blood flow and neuronal activation, the so-called neurovascular coupling. Combined with experimental techniques only available in animal models, such as intracerebral micro-stimulation, optogenetics or pharmacogenetics, provides a powerful framework to investigate the impact of specific circuit manipulations on overall brain dynamics. The purpose of this chapter is to provide a comprehensive protocol to measure brain activity using fMRI with intracerebral electric micro-stimulation in murine models. Preclinical research (especially in rodents) opens the door to very sophisticated and informative experiments, but at the same time imposes important constrains (i.e., anesthetics, translatability), some of which will be addressed here.

Key words

fMRI BOLD Intracerebral micro-stimulation Preclinical MRI 

Notes

Acknowledgements

This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER funds under grants BFU2015-64380-C2-1-R (S.C.) and BFU2015-64380-C2-2-R (D.M.) and EU Horizon 2020 Program 668863-SyBil-AA grant (S.C.). S.C. acknowledges financial support from the Spanish State Research Agency, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (ref. SEV- 2013-0317).

References

  1. 1.
    Crosson B, Ford A, McGregor KM, Meinzer M, Cheshkov S, Li X, Walker-Batson D, Briggs RW (2010) Functional imaging and related techniques: an introduction for rehabilitation researchers. J Rehabil Res Dev 47(2):vii–xxxivCrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 87(24):9868–9872CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453(7197):869–878. https://doi.org/10.1038/nature06976 CrossRefPubMedGoogle Scholar
  4. 4.
    Moreno A, Jego P, de la Cruz F, Canals S (2013) Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals. Front Neuroenerg 5:3. https://doi.org/10.3389/fnene.2013.00003 CrossRefGoogle Scholar
  5. 5.
    Jego P, Pacheco-Torres J, Araque A, Canals S (2014) Functional MRI in mice lacking IP3-dependent calcium signaling in astrocytes. J Cereb Blood Flow Metab 34(10):1599–1603. https://doi.org/10.1038/jcbfm.2014.144 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Greve JM (2011) The BOLD effect. Methods Mol Biol 771:153–169. https://doi.org/10.1007/978-1-61779-219-9_8 CrossRefPubMedGoogle Scholar
  7. 7.
    Masamoto K, Kanno I (2012) Anesthesia and the quantitative evaluation of neurovascular coupling. J Cereb Blood Flow Metab 32(7):1233–1247. https://doi.org/10.1038/jcbfm.2012.50 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Khubchandani M, Mallick HN, Jagannathan NR, Mohan Kumar V (2003) Stereotaxic assembly and procedures for simultaneous electrophysiological and MRI study of conscious rat. Magn Reson Med 49(5):962–967. https://doi.org/10.1002/mrm.10441 CrossRefPubMedGoogle Scholar
  9. 9.
    King JA, Garelick TS, Brevard ME, Chen W, Messenger TL, Duong TQ, Ferris CF (2005) Procedure for minimizing stress for fMRI studies in conscious rats. J Neurosci Methods 148(2):154–160. https://doi.org/10.1016/j.jneumeth.2005.04.011 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ferris CF, Febo M, Luo F, Schmidt K, Brevard M, Harder JA, Kulkarni P, Messenger T, King JA (2006) Functional magnetic resonance imaging in conscious animals: a new tool in behavioural neuroscience research. J Neuroendocrinol 18(5):307–318. https://doi.org/10.1111/j.1365-2826.2006.01424.x CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tennant DA, Duran RV, Gottlieb E (2010) Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 10(4):267–277. https://doi.org/10.1038/nrc2817 CrossRefPubMedGoogle Scholar
  12. 12.
    European Convention for the Protection of vertebrate animals used for experimental and other scientific purposes (2006) Appendix A. Guidelines for accommodation and care of animals (Article 5 of the Convention)Google Scholar
  13. 13.
    Hendrich KS, Kochanek PM, Melick JA, Schiding JK, Statler KD, Williams DS, Marion DW, Ho C (2001) Cerebral perfusion during anesthesia with fentanyl, isoflurane, or pentobarbital in normal rats studied by arterial spin-labeled MRI. Magn Reson Med 46(1):202–206CrossRefPubMedGoogle Scholar
  14. 14.
    Schroeter A, Schlegel F, Seuwen A, Grandjean J, Rudin M (2014) Specificity of stimulus-evoked fMRI responses in the mouse: the influence of systemic physiological changes associated with innocuous stimulation under four different anesthetics. NeuroImage 94:372–384. https://doi.org/10.1016/j.neuroimage.2014.01.046 CrossRefPubMedGoogle Scholar
  15. 15.
    Sonnay S, Just N, Duarte JM, Gruetter R (2015) Imaging of prolonged BOLD response in the somatosensory cortex of the rat. NMR Biomed 28(3):414–421. https://doi.org/10.1002/nbm.3263 CrossRefPubMedGoogle Scholar
  16. 16.
    Paasonen J, Salo RA, Shatillo A, Forsberg MM, Narvainen J, Huttunen JK, Grohn O (2016) Comparison of seven different anesthesia protocols for nicotine pharmacologic magnetic resonance imaging in rat. Eur Neuropsychopharmacol 26(3):518–531. https://doi.org/10.1016/j.euroneuro.2015.12.034 CrossRefPubMedGoogle Scholar
  17. 17.
    Maggi CA, Meli A (1986) Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system. Experientia 42(3):292–297CrossRefPubMedGoogle Scholar
  18. 18.
    Moreno A, Morris RG, Canals S (2016) Frequency-dependent gating of hippocampal-neocortical interactions. Cereb Cortex 26(5):2105–2114. https://doi.org/10.1093/cercor/bhv033 CrossRefPubMedGoogle Scholar
  19. 19.
    Pawela CP, Biswal BB, Hudetz AG, Schulte ML, Li R, Jones SR, Cho YR, Matloub HS, Hyde JS (2009) A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity. NeuroImage 46(4):1137–1147. https://doi.org/10.1016/j.neuroimage.2009.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Shyu BC, Lin CY, Sun JJ, Sylantyev S, Chang C (2004) A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode. J Neurosci Methods 137(1):123–131. https://doi.org/10.1016/j.jneumeth.2004.02.015 CrossRefPubMedGoogle Scholar
  21. 21.
    Sultan F, Augath M, Murayama Y, Tolias AS, Logothetis N (2011) esfMRI of the upper STS: further evidence for the lack of electrically induced polysynaptic propagation of activity in the neocortex. Magn Reson Imaging 29(10):1374–1381. https://doi.org/10.1016/j.mri.2011.04.005 CrossRefPubMedGoogle Scholar
  22. 22.
    Alvarez-Salvado E, Pallares V, Moreno A, Canals S (2014) Functional MRI of long-term potentiation: imaging network plasticity. Philos Trans R Soc Lond Ser B Biol Sci 369(1633):20130152. https://doi.org/10.1098/rstb.2013.0152 CrossRefGoogle Scholar
  23. 23.
    Canals S, Beyerlein M, Murayama Y, Logothetis NK (2008) Electric stimulation fMRI of the perforant pathway to the rat hippocampus. Magn Reson Imaging 26(7):978–986. https://doi.org/10.1016/j.mri.2008.02.018 CrossRefPubMedGoogle Scholar
  24. 24.
    Godino Mdel C, Romera VG, Sanchez-Tomero JA, Pacheco J, Canals S, Lerma J, Vivancos J, Moro MA, Torres M, Lizasoain I, Sanchez-Prieto J (2013) Amelioration of ischemic brain damage by peritoneal dialysis. J Clin Invest 123(10):4359–4363. https://doi.org/10.1172/JCI67284 CrossRefPubMedGoogle Scholar
  25. 25.
    Hadar R, Vengeliene V, Barroeta Hlusicke E, Canals S, Noori HR, Wieske F, Rummel J, Harnack D, Heinz A, Spanagel R, Winter C (2016) Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens. Transl Psychiatry 6(6):e840. https://doi.org/10.1038/tp.2016.100 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Tehovnik EJ, Tolias AS, Sultan F, Slocum WM, Logothetis NK (2006) Direct and indirect activation of cortical neurons by electrical microstimulation. J Neurophysiol 96(2):512–521. https://doi.org/10.1152/jn.00126.2006 CrossRefPubMedGoogle Scholar
  27. 27.
    Pallares V, Moya J, Samper-Belda FJ, Canals S, Moratal D (2015) Neurosurgery planning in rodents using a magnetic resonance imaging assisted framework to target experimentally defined networks. Comput Methods Prog Biomed 121(2):66–76. https://doi.org/10.1016/j.cmpb.2015.05.011 CrossRefGoogle Scholar
  28. 28.
    Eklund A, Nichols TE, Knutsson H (2016) Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates. Proc Natl Acad Sci U S A 113(28):7900–7905. https://doi.org/10.1073/pnas.1602413113 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Poldrack RA, Mumford JA, Nichols TE (2011) Handbook of functional MRI data analysis. Cambridge University Press, New YorkCrossRefGoogle Scholar
  30. 30.
    Ashby FG (2011) Statistical analysis of FMRI Data. MIT Press, Cambridge, MAGoogle Scholar
  31. 31.
    Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, Elsevier, New YorkGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Laura Pérez-Cervera
    • 1
  • José María Caramés
    • 1
  • Luis Miguel Fernández-Mollá
    • 2
  • Andrea Moreno
    • 1
    • 2
  • Begoña Fernández
    • 1
  • Elena Pérez-Montoyo
    • 1
  • David Moratal
    • 2
  • Santiago Canals
    • 1
  • Jesús Pacheco-Torres
    • 1
  1. 1.Instituto de NeurocienciasConsejo Superior de Investigaciones Científicas, Universidad Miguel HernándezSant Joan d’AlacantSpain
  2. 2.Center for Biomaterials and Tissue EngineeringUniversitat Politècnica de ValènciaValenciaSpain

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