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.
References
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–xxxiv
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):9868–9872
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
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
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
Greve JM (2011) The BOLD effect. Methods Mol Biol 771:153–169. https://doi.org/10.1007/978-1-61779-219-9_8
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
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
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
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
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
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)
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):202–206
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
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
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
Maggi CA, Meli A (1986) Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system. Experientia 42(3):292–297
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
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
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
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
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
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
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
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
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
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
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
Poldrack RA, Mumford JA, Nichols TE (2011) Handbook of functional MRI data analysis. Cambridge University Press, New York
Ashby FG (2011) Statistical analysis of FMRI Data. MIT Press, Cambridge, MA
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, Elsevier, New York
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).
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Pérez-Cervera, L. et al. (2018). Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation fMRI. In: García Martín, M., López Larrubia, P. (eds) Preclinical MRI. Methods in Molecular Biology, vol 1718. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7531-0_8
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