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Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons

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Listed:
  • P. Dylan Rich

    (Princeton University)

  • Stephan Yves Thiberge

    (Princeton University)

  • Benjamin B. Scott

    (Boston University
    Boston University
    Boston University)

  • Caiying Guo

    (Janelia Research Campus
    Howard Hughes Medical Institute)

  • D. Gowanlock R. Tervo

    (Janelia Research Campus
    Howard Hughes Medical Institute)

  • Carlos D. Brody

    (Princeton University
    Princeton University)

  • Alla Y. Karpova

    (Janelia Research Campus
    Howard Hughes Medical Institute)

  • Nathaniel D. Daw

    (Princeton University
    Princeton University)

  • David W. Tank

    (Princeton University
    Princeton University
    Princeton University)

Abstract

The precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory are not fully understood. Two-photon calcium imaging allows the activity of individual cells to be followed across long periods, but conventional approaches require head-fixation, which limits the type of behavior that can be studied. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous systems that used mechanical restraint, there are no moving parts and animals can engage and disengage entirely at will. This system is failsafe, easy for animals to use and reliable enough to allow long-term experiments to be routinely performed. Animals completed hundreds of trials per session of an odor discrimination task that required 2–4 s fixations. Together with a reflectance fluorescence collection scheme that increases two-photon signal and a transgenic Thy1-GCaMP6f rat line, we are able to reliably image the cellular activity in the hippocampus during behavior over long periods (median 6 months), allowing us track the same neurons over a large fraction of animals’ lives (up to 19 months).

Suggested Citation

  • P. Dylan Rich & Stephan Yves Thiberge & Benjamin B. Scott & Caiying Guo & D. Gowanlock R. Tervo & Carlos D. Brody & Alla Y. Karpova & Nathaniel D. Daw & David W. Tank, 2024. "Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48505-9
    DOI: 10.1038/s41467-024-48505-9
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    References listed on IDEAS

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