Skip to main content
SpringerLink
Log in

Quantitative activity-induced manganese-dependent MRI for characterizing cortical layers in the primary somatosensory cortex of the rat

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

The ability of Mn2+ to follow Ca2+ pathways upon stimulation transform them into remarkable surrogate markers of neuronal activity using activity-induced manganese-dependent MRI (AIM–MRI). In the present study, a precise follow-up of physiological parameters during MnCl2 and mannitol infusions improved the reproducibility of AIM–MRI allowing in-depth evaluation of the technique. Pixel-by-pixel T1 data were investigated using histogram distributions in the barrel cortex (BC) and the thalamus before and after Mn2+ infusion, after blood brain barrier opening and after BC activation. Mean BC T1 values dropped significantly upon trigeminal nerve (TGN) stimulation (−38 %, P = 0.02) in accordance with previous literature findings. T1 histogram distributions showed that 34 % of T1s in the range 600–1500 ms after Mn2+ + mannitol infusions shifted to 50–350 ms after TGN stimulation corresponding to a twofold increase of the percentage of pixels with the lowest T1s in BC. Moreover, T1 changes in response to stimulation increased significantly from superficial cortical layers (I–III) to deeper layers (V–VI). Cortical cytoarchitecture detection during a functional paradigm was performed extending the potential of AIM–MRI. Quantitative AIM–MRI could thus offer a means to interpret local neural activity across cortical layers while identification of the role of calcium dynamics in vivo during brain activation could play a key role in resolving neurovascular coupling mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aoki I, Tanaka C, Takegami T, Ebisu T, Umeda M, Fukunaga M, Fukuda K, Silva AC, Koretsky AP, Naruse S (2002) Dynamic activity-induced manganese-dependent contrast magnetic resonance imaging (DAIM MRI). Magn Reson Med 48(6):927–933

    Article  CAS  PubMed  Google Scholar 

  • Aoki I, Naruse S, Tanaka C (2004) Manganese-enhanced magnetic resonance imaging (MEMRI) of brain activity and applications to early detection of brain ischemia. NMR Biomed 17(8):569–580

    Article  CAS  PubMed  Google Scholar 

  • Benedetti B, Matyash V, Kettenmann H (2011) Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex. J Physiol 589(Pt 5):1159–1172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuang KH, Lee JH, Silva AC, Belluscio L, Koretsky AP (2009) Manganese enhanced MRI reveals functional circuitry in response to odorant stimuli. Neuroimage 44(2):363–372

    Article  PubMed  PubMed Central  Google Scholar 

  • Duong TQ, Silva AC, Lee SP, Kim SG (2000) Functional MRI of calcium-dependent synaptic activity: cross correlation with CBF and BOLD measurements. Magn Reson Med 43(3):383–392

    Article  CAS  PubMed  Google Scholar 

  • Egger V, Feldmeyer D, Sakmann B (1999) Coincidence detection and changes of synaptic efficacy in spiny stellate neurons in rat barrel cortex. Nat Neurosci 2(12):1098–1105

    Article  CAS  PubMed  Google Scholar 

  • Fa Z, Zhang R, Li P, Zhang J, Zhang P, Zhu S, Wu Q, Huang F, Liu Y, Yang L, Chang H, Wen Z, Gao D, Zeng Y, Jiang X (2011) Effects of temporarily disrupting BBB on activity-induced manganese-dependent functional MRI. Brain Imaging Behav 5(3):181–188

    Article  PubMed  Google Scholar 

  • Helmchen F, Svoboda K, Denk W, Tank DW (1999) In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nat Neurosci 2(11):989–996

    Article  CAS  PubMed  Google Scholar 

  • Herman P, Sanganahalli BG, Blumenfeld H, Rothman DL, Hyder F (2013) Quantitative basis for neuroimaging of cortical laminae with calibrated functional MRI. Proc Natl Acad Sci U S A. 110(37):15115–15120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue T, Majid T, Pautler RG (2011) Manganese enhanced MRI (MEMRI): neurophysiological applications. Rev Neurosci 22(6):675–694

    Article  PubMed  PubMed Central  Google Scholar 

  • Just N, Gruetter R (2011) Detection of neuronal activity and metabolism in a model of dehydration-induced anorexia in rats at 14.1 T using manganese-enhanced MRI and 1H MRS. NMR Biomed 24(10):1326–1336

    Article  CAS  PubMed  Google Scholar 

  • Just N, Petersen C, Gruetter R (2010) BOLD responses to trigeminal nerve stimulation. Magn Reson Imaging 28(8):1143–1151

    Article  PubMed  Google Scholar 

  • Just N, Cudalbu C, Lei H, Gruetter R (2011) Effect of manganese chloride on the neurochemical profile of the rat hypothalamus. J Cereb Blood Flow Metab 31(12):2324–2333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Just N, Xin L, Frenkel H, Gruetter R (2013) Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences. Neuroimage 74:343–351

    Article  PubMed  Google Scholar 

  • Koretsky AP, Silva AC (2004) Manganese-enhanced magnetic resonance imaging (MEMRI). NMR Biomed 17(8):527–531

    Article  CAS  PubMed  Google Scholar 

  • Lauritzen M (2005) Reading vascular changes in brain imaging: is dendritic calcium the key? Nat Rev Neurosci 6(1):77–85

    Article  CAS  PubMed  Google Scholar 

  • Lecrux C, Toussay X, Kocharyan A, Fernandes P, Neupane S, Lévesque M, Plaisier F, Shmuel A, Cauli B (2011) Hamel E Pyramidal neurons are “neurogenic hubs” in the neurovascular coupling response to whisker stimulation. J Neurosci 31(27):9836–9847

    Article  CAS  PubMed  Google Scholar 

  • Lin YJ, Koretsky AP (1997) Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn Reson Med 38(3):378–388

    Article  CAS  PubMed  Google Scholar 

  • Lu H, Patel S, Luo F, Li SJ, Hillard CJ, Ward BD, Hyde JS (2004) Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression. Magn Reson Med 52(5):1060–1068

    Article  PubMed  Google Scholar 

  • Marques JP, Gruetter R (2013) New developments and applications of the MP2RAGE sequence–focusing the contrast and high spatial resolution R1 mapping. PLoS One 8(7):e69294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mlynárik V, Gambarota G, Frenkel H, Gruetter R (2006) Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition. Magn Reson Med 56(5):965–970

    Article  PubMed  Google Scholar 

  • Nevian T, Sakmann B (2004) Single spine Ca2 + signals evoked by coincident EPSPs and backpropagating action potentials in spiny stellate cells of layer 4 in the juvenile rat somatosensory barrel cortex. J Neurosci 24(7):1689–1699

    Article  CAS  PubMed  Google Scholar 

  • Norup Nielsen A, Lauritzen M (2001) Coupling and uncoupling of activity-dependent increases of neuronal activity and blood flow in rat somatosensory cortex. J Physiol 533(Pt 3):773–785

    Article  CAS  PubMed  Google Scholar 

  • Nuñez A, Domínguez S, Buño W, Fernández de Sevilla D (2012) Cholinergic-mediated response enhancement in barrel cortex layer V pyramidal neurons. J Neurophysiol 108(6):1656–1668

    Article  PubMed  Google Scholar 

  • O’Connor DH, Peron SP, Huber D, Svoboda K (2010) Neural activity in barrel cortex underlying vibrissa-based object localization in mice. Neuron 67(6):1048–1061

    Article  PubMed  Google Scholar 

  • Parker GJ, Baustert I, Tanner SF, Leach MO (2000) Improving image quality and T(1) measurements using saturation recovery turboFLASH with an approximate K-space normalisation filter. Magn Reson Imaging 18(2):157–167

    Article  CAS  PubMed  Google Scholar 

  • Pautler RG (2006) Biological applications of manganese-enhanced magnetic resonance imaging. Methods Mol Med 124:365–386

    CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  • Schulz K, Sydekum E, Krueppel R, Engelbrecht CJ, Schlegel F, Schröter A, Rudin M, Helmchen F (2012) Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex. Nat Methods 9(6):597–602

    Article  CAS  PubMed  Google Scholar 

  • Serrano F, Deshazer M, Smith KD, Ananta JS, Wilson LJ, Pautler RG (2008) Assessing transneuronal dysfunction utilizing manganese-enhanced MRI (MEMRI). Magn Reson Med 60(1):169–175

    Article  PubMed  Google Scholar 

  • Shih YY, Chen YY, Lai HY, Kao YC, Shyu BC, Duong TQ (2013) Ultra high-resolution fMRI and electrophysiology of the rat primary somatosensory cortex. Neuroimage 73:113–120

    Article  PubMed  PubMed Central  Google Scholar 

  • Silva AC, Lee JH, Wu CW, Tucciarone J, Pelled G, Aoki I, Koretsky AP (2008) Detection of cortical laminar architecture using manganese-enhanced MRI. J Neurosci Methods 167(2):246–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci USA 100(12):7319–7324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Svoboda K, Helmchen F, Denk W, Tank DW (1999) Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo. Nat Neurosci 2(1):65–73

    Article  CAS  PubMed  Google Scholar 

  • Tucciarone J, Chuang KH, Dodd SJ, Silva A, Pelled G, Koretsky AP (2009) Layer specific tracing of corticocortical and thalamocortical connectivity in the rodent using manganese enhanced MRI. Neuroimage 44:923–931

    Article  PubMed  Google Scholar 

  • Van der Linden A, Van Meir V, Tindemans I, Verhoye M, Balthazart J (2004) Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds. NMR Biomed 17(8):602–612

    Article  PubMed  Google Scholar 

  • Wang X, Lou N, Xu Q, Tian GF, Peng WG, Han X, Kang J, Takano T, Nedergaard M (2006) Astrocytic Ca2+signaling evoked by sensory stimulation in vivo. Nat Neurosci 9(6):816–823

    Article  CAS  PubMed  Google Scholar 

  • Weng JC, Chen JH, Yang PF, Tseng WY (2007) Functional mapping of rat barrel activation following whisker stimulation using activity-induced manganese-dependent contrast. Neuroimage 36(4):1179–1188

    Article  PubMed  Google Scholar 

  • Yu X, Chung S, Chen DY, Wang S, Dodd SJ, Walters JR, Isaac JT, Koretsky AP (2012a) Thalamocortical inputs show post-critical-period plasticity. Neuron 74(4):731–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Glen D, Wang S, Dodd S, Hirano Y, Saad Z, Reynolds R, Silva AC (2012b) Koretsky AP Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV–V of the rat whisker-barrel cortex. Neuroimage 59(2):1451–1460

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu X, Qian C, Chen DY, Dodd SJ, Koretsky AP (2014) Deciphering laminar-specific neural inputs with line-scanning fMRI. Nat Methods 11(1):55–58

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang R, Fa Z, Liu Y, Sun H, Li P, Li S, Wang X, Lei H, Jiang X (2014) Dynamic MRI of rat brain following manganese administration through the internal carotid artery. Neurol Res 36(7):679–686. doi:10.1179/1743132813Y.0000000291

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Centre d’Imagerie BioMédicale (CIBM) of Ecole Polytechnique Fédérale de Lausanne (EPFL), the University of Lausanne (UNIL) and the Foundations Leenards et Jeantet. The authors would like to acknowledge strong technical support from Dr Mario Lepore and Hanne Frenkel from the CIBM veterinary team.

Conflict of interest

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Laboratory for Functional and Metabolic Imaging (LIFMET), Centre d’Imagerie Biomédicale-Animal Imaging and Technology Core (CIBM-AIT), Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland

    Matthieu Auffret, Idrees Samim, Mario Lepore, Rolf Gruetter & Nathalie Just

Authors
  1. Matthieu Auffret
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Idrees Samim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario Lepore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rolf Gruetter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathalie Just
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathalie Just.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Auffret, M., Samim, I., Lepore, M. et al. Quantitative activity-induced manganese-dependent MRI for characterizing cortical layers in the primary somatosensory cortex of the rat. Brain Struct Funct 221, 695–707 (2016). https://doi.org/10.1007/s00429-014-0933-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-014-0933-3

Keywords

Search

Navigation