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

Authors

Yu Liu
Samuel S McAfee
Meike E Van Der Heijden
Mukesh Dhamala
Roy V Sillitoe
Detlef H Heck

Publication Date

10-1-2022

Journal

Cerebellum

DOI

10.1007/s12311-022-01383-7

PMID

35218525

PMCID

PMC10230449

PubMedCentral® Posted Date

5-31-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Cerebellar Cortex, Hippocampus, Memory, Short-Term, Mice, Prefrontal Cortex, Spatial Memory, Spatial working memory, Decision-making, Neuronal communication, Cerebellum, Prefrontal cortex, Hippocampus, Coherence, Cognition, Purkinje cell, Medial prefrontal cortex, Electrophysiology, Optogenetics

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.