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

P. Dylan Rich (), Stephan Yves Thiberge, Benjamin B. Scott, Caiying Guo, D. Gowanlock R. Tervo, Carlos D. Brody, Alla Y. Karpova, Nathaniel D. Daw and David W. Tank ()
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P. Dylan Rich: Princeton University
Stephan Yves Thiberge: Princeton University
Benjamin B. Scott: Boston University
Caiying Guo: Janelia Research Campus
D. Gowanlock R. Tervo: Janelia Research Campus
Carlos D. Brody: Princeton University
Alla Y. Karpova: Janelia Research Campus
Nathaniel D. Daw: Princeton University
David W. Tank: Princeton University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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).

Date: 2024
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DOI: 10.1038/s41467-024-48505-9

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