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Causal Evidence for a Role of Cerebellar Lobulus Simplex in Prefrontal-Hippocampal Interaction in Spatial Working Memory Decision-Making

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Abstract

Spatial working memory (SWM) is a cerebrocerebellar cognitive skill supporting survival-relevant behaviors, such as optimizing foraging behavior by remembering recent routes and visited sites. It is known that SWM decision-making in rodents requires the medial prefrontal cortex (mPFC) and dorsal hippocampus. The decision process in SWM tasks carries a specific electrophysiological signature of a brief, decision-related increase in neuronal communication in the form of an increase in the coherence of neuronal theta oscillations (4–12 Hz) between the mPFC and dorsal hippocampus, a finding we replicated here during spontaneous exploration of a plus maze in freely moving mice. We further evaluated SWM decision-related coherence changes within frequency bands above theta. Decision-related coherence increases occurred in seven frequency bands between 4 and 200 Hz and decision-outcome–related differences in coherence modulation occurred within the beta and gamma frequency bands and in higher frequency oscillations up to 130 Hz. With recent evidence that Purkinje cells in the cerebellar lobulus simplex (LS) represent information about the phase and phase differences of gamma oscillations in the mPFC and dorsal hippocampus, we hypothesized that LS might be involved in the modulation of mPFC-hippocampal gamma coherence. We show that optical stimulation of LS significantly impairs SWM performance and decision-related mPFC-dCA1 coherence modulation, providing causal evidence for an involvement of cerebellar LS in SWM decision-making at the behavioral and neuronal level. Our findings suggest that the cerebellum might contribute to SWM decision-making by optimizing the decision-related modulation of mPFC-dCA1 coherence.

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Acknowledgements

We would like to thank the Neuroscience Institute of the University of Tennessee Health Science Center (UTHSC) for the financial support, Micheal Nguyen from the UTHSC Bio-Medical Services and Shuhua Qi for technical support. We would also like to thank Amanda Brown and Trace Stay (Baylor College of Medicine) for the support with some of the breeding and also for genotyping. DHH and YL are supported by R01MH112143, R01MH112143-02S1, and R37MH085726. RVS is supported by R01NS100874, R01NS119301, R01MH112143, and U54HD083092.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Tennessee HSC, Memphis, TN, USA

    Yu Liu & Detlef H. Heck

  2. Department of Diagnostic Imaging, St Jude Children’s Research Hospital, Memphis, TN, USA

    Samuel S. McAfee

  3. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Meike E. Van Der Heijden & Roy V. Sillitoe

  4. Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, Houston, TX, USA

    Meike E. Van Der Heijden & Roy V. Sillitoe

  5. Department of Physics and Astronomy, Neuroscience Institute, Georgia State University, Atlanta, GA, USA

    Mukesh Dhamala

  6. Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA

    Roy V. Sillitoe

  7. Development, Disease Models & Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX, USA

    Roy V. Sillitoe

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  1. Yu Liu
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  4. Mukesh Dhamala
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Contributions

Conceptualization: DHH, SSM, RVS, YL. Formal analysis: YL, SSM, and MD. Funding acquisition: DHH and RVS. Methodology: YL. Supervision: DHH. Writing – original draft: YL and DHH. Writing – review and editing: DHH, YL, SSM, MEvdH, MD, RVS.

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Correspondence to Detlef H. Heck.

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Liu, Y., McAfee, S.S., Van Der Heijden, M.E. et al. Causal Evidence for a Role of Cerebellar Lobulus Simplex in Prefrontal-Hippocampal Interaction in Spatial Working Memory Decision-Making. Cerebellum 21, 762–775 (2022). https://doi.org/10.1007/s12311-022-01383-7

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