Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation fMRI
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 wordsfMRI BOLD Intracerebral micro-stimulation Preclinical MRI
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).
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 30.Ashby FG (2011) Statistical analysis of FMRI Data. MIT Press, Cambridge, MAGoogle Scholar
- 31.Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, Elsevier, New YorkGoogle Scholar