Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors

Joon-Hyuk Lee, Chong Guo, Shuting Wu, Aliya Norton, Soobin Seo, Zhiyi Yao and Wade G. Regehr ()
Additional contact information
Joon-Hyuk Lee: Harvard Medical School
Chong Guo: Harvard Medical School
Shuting Wu: Harvard Medical School
Aliya Norton: Harvard Medical School
Soobin Seo: Harvard Medical School
Zhiyi Yao: Harvard Medical School
Wade G. Regehr: Harvard Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Mossy fiber inputs are transformed into cerebellar Purkinje cell (PC) outputs by granule cell (GC)-dependent processing. Cerebellar dysfunction leads to motor, learning, emotional, and social deficits that are usually attributed to altered PC firing arising from impaired processing of mossy fiber inputs, even though PCs also fire independently of GCs. To isolate their contributions to cerebellum-dependent behaviors, we either disrupt GC signaling while leaving PC firing intact, or disrupt PC signaling to eliminate the influence of PCs. Experiments were performed in mice of both sexes. We find that both GC and PC signaling are essential for eyeblink conditioning and vestibulo-ocular reflex (VOR) learning. Remarkably, disrupting PC signaling impairs VOR, anxiety, and social behavior, but abolishing GC signaling does not. This establishes that while GC signaling is critical for motor learning, it does not influence many behaviors including those associated with autism-spectrum disorder. It suggests that GC-independent behaviors can potentially be rescued by restoring altered firing in downstream regions.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61190-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61190-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61190-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().