HippoBellum: Acute cerebellar modulation alters hippocampal dynamics and function

Zachary Zeidler, Katerina Hoffmann, Esther Krook-Magnuson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Here we examine what effects acute manipulation of the cerebellum, a canonically motor structure, can have on the hippocampus, a canonically cognitive structure. In male and female mice, acute perturbation of the cerebellar vermis (lobule 4/5) or simplex produced reliable and specific effects in hippocampal function at cellular, population, and behavioral levels, including evoked local field potentials, increased hippocampal cFos expression, and altered CA1 calcium event rate, amplitudes, and correlated activity. We additionally noted a selective deficit on an object location memory task, which requires objection-location pairing. We therefore combined cerebellar optogenetic stimulation and CA1 calcium imaging with an object-exploration task, and found that cerebellar stimulation reduced the representation of place fields near objects, and prevented a shift in representation to the novel location when an object was moved. Together, these results clearly demonstrate that acute modulation of the cerebellum alters hippocampal function, and further illustrates that the cerebellum can influence cognitive domains.

Original languageEnglish (US)
Pages (from-to)6910-6926
Number of pages17
JournalJournal of Neuroscience
Volume40
Issue number36
DOIs
StatePublished - Sep 2 2020

Bibliographical note

Funding Information:
This work (and the E.K.-M. laboratory) was supported by Winston and Maxine Wallin Neuroscience Discovery Fund to E.K.-M.; National Institutes of Health Grants R00NS087110, R01NS104071, and R01NS112518 to E.K.-M.; National Institute of Neurological Disorders and Stroke 1F31NS103320 to Z.Z.; University of Minnesota MnDRIVE (Minnesota’s Discovery, Research and Innovation Economy) initiative and Informatics Institute to E.K.-M. and Z.Z.; and McKnight Land-Grant Professorship to E.K.-M. GCaMP6f was developed by the GENIE Program and the Janelia Farm Research Campus, specifically Drs. Vivek Jayaraman, Rex A. Kerr, Douglas S. Kim, Loren L. Looger, and Karel Svoboda. We thank the entire E.K.-M. laboratory, especially Zachary Montes for assistance with behavioral testing, Shabad Washist for immunohistochemical processing, Chris Krook-Magnuson for development of LFP analysis software, Tom Richner for coding assistance, and Isaac Hoff for colony management; A. David Redish for discussions of place cells and experimental design; and Michael Benneyworth and the University of Minnesota Mouse Behavior Core, Mark Sanders and the University of Minnesota University Imaging Center, and Peyman Golshani and the University of California Los Angeles Miniscope project for providing open-source materials and hosting their workshop. The authors declare no competing financial interests. Correspondence should be addressed to Zachary Zeidler at zeidl012@umn.edu. https://doi.org/10.1523/JNEUROSCI.0763-20.2020 Copyright © 2020 the authors

Keywords

  • Cerebellum
  • Hippocampus
  • Miniscope
  • Object memory
  • Spatial memory

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