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Brain Structure and Function

, Volume 220, Issue 4, pp 2043–2057 | Cite as

Whole-brain mapping of behaviourally induced neural activation in mice

  • Dulcie A. VousdenEmail author
  • Jonathan Epp
  • Hiroyuki Okuno
  • Brian J. Nieman
  • Matthijs van Eede
  • Jun Dazai
  • Timothy Ragan
  • Haruhiko Bito
  • Paul W. Frankland
  • Jason P. Lerch
  • R. Mark Henkelman
Original Article

Abstract

The ability to visualize behaviourally evoked neural activity patterns across the rodent brain is essential for understanding the distributed brain networks mediating particular behaviours. However, current imaging methods are limited in their spatial resolution and/or ability to obtain brain-wide coverage of functional activity. Here, we describe a new automated method for obtaining cellular-level, whole-brain maps of behaviourally induced neural activity in the mouse. This method combines the use of transgenic immediate-early gene reporter mice to visualize neural activity; serial two-photon tomography to image the entire brain at cellular resolution; advanced image processing algorithms to count the activated neurons and align the datasets to the Allen Mouse Brain Atlas; and statistical analysis to identify the network of activated brain regions evoked by behaviour. We demonstrate the use of this approach to determine the whole-brain networks activated during the retrieval of fear memories. Consistent with previous studies, we identified a large network of amygdalar, hippocampal, and neocortical brain regions implicated in fear memory retrieval. Our proposed methods can thus be used to map cellular networks involved in the expression of normal behaviours as well as to investigate in depth circuit dysfunction in mouse models of neurobiological disease.

Keywords

Neuroimaging Immediate-early genes Memory Functional networks Serial two-photon tomography 

Notes

Acknowledgments

Research was supported by the Canadian Foundation for Innovation, Canadian Institute for Health Research (CIHR), Natural Science and Engineering Research Council (NSERC-DV), Ontario Research Foundation, a CREST-JST grant (HB and HO), and by Grants-in-Aid from JSPS (KIBAN to HO, WAKATE to HB) and from MHLW of Japan (to HB and HO). RMH was supported by a Canada Research Chair.

Conflict of interest

TR is a shareholder and employee of TissueVision, Inc.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Dulcie A. Vousden
    • 1
    • 2
    • 4
    Email author
  • Jonathan Epp
    • 2
  • Hiroyuki Okuno
    • 5
  • Brian J. Nieman
    • 1
    • 3
    • 4
  • Matthijs van Eede
    • 1
  • Jun Dazai
    • 1
  • Timothy Ragan
    • 7
  • Haruhiko Bito
    • 5
  • Paul W. Frankland
    • 2
    • 6
    • 8
  • Jason P. Lerch
    • 1
    • 2
    • 4
  • R. Mark Henkelman
    • 1
    • 3
    • 4
  1. 1.Mouse Imaging CentreThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Program in Neuroscience and Mental HealthThe Hospital for Sick ChildrenTorontoCanada
  3. 3.Program in Physiology and Experimental MedicineThe Hospital for Sick ChildrenTorontoCanada
  4. 4.Department of Medical BiophysicsUniversity of TorontoTorontoCanada
  5. 5.Department of NeurochemistryThe University of Tokyo Graduate School of Medicine, CREST-JSTTokyoJapan
  6. 6.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  7. 7.TissueVision, Inc.CambridgeUSA
  8. 8.Department of PhysiologyUniversity of TorontoTorontoCanada

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