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Nat. Commun., Published: 02 July 2025 | https://doi.org/10.1038/s41467-025-61190-6
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 & Wade G. Regehr
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Corresponding author
Correspondence to Wade G. Regehr.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Corresponding author
Correspondence to Wade G. Regehr.
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.
논문정보
- Research article
- 2025년 07월 (BRIC 등록일 2025-07-04)
- 국외 연구진
- 생명과학 > 신경생물학
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