4.4 Article

Functional Convergence of Motor and Social Processes in Lobule IV/V of the Mouse Cerebellum

Journal

CEREBELLUM
Volume 20, Issue 6, Pages 836-852

Publisher

SPRINGER
DOI: 10.1007/s12311-021-01246-7

Keywords

Cerebellum; Lesion; Chemogenetics; Object recognition; Social memory; Functional connectivity

Categories

Funding

  1. National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) [R15NS112964]
  2. Winston and Maxine Wallin Neuroscience Discovery Fund
  3. University of Minnesota
  4. DFG [HU 306/27-3]

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Disruption of activity in the major anterior lobule IV/V in mice impaired motor coordination but not general locomotion or anxiety-related behavior. Lesioned animals showed memory deficits, while chemogenetic excitation of Purkinje cells affected social approach and social memory.
Topographic organization of the cerebellum is largely segregated into the anterior and posterior lobes that represent its motor and non-motor functions, respectively. Although patients with damage to the anterior cerebellum often exhibit motor deficits, it remains unclear whether and how such an injury affects cognitive and social behaviors. To address this, we perturbed the activity of major anterior lobule IV/V in mice by either neurotoxic lesion or chemogenetic excitation of Purkinje cells in the cerebellar cortex. We found that both of the manipulations impaired motor coordination, but not general locomotion or anxiety-related behavior. The lesioned animals showed memory deficits in object recognition and social-associative recognition tests, which were confounded by a lack of exploration. Chemogenetic excitation of Purkinje cells disrupted the animals' social approach in a less-preferred context and social memory, without affecting their overall exploration and object-based memory. In a free social interaction test, the two groups exhibited less interaction with a stranger conspecific. Subsequent c-Fos imaging indicated that decreased neuronal activities in the medial prefrontal cortex, hippocampal dentate gyrus, parahippocampal cortices, and basolateral amygdala, as well as disorganized modular structures of the brain networks might underlie the reduced social interaction. These findings suggest that the anterior cerebellum plays an intricate role in processing motor, cognitive, and social functions.

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