Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors
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...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61190-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849402147385376768 |
|---|---|
| author | Joon-Hyuk Lee Chong Guo Shuting Wu Aliya Norton Soobin Seo Zhiyi Yao Wade G. Regehr |
| author_facet | Joon-Hyuk Lee Chong Guo Shuting Wu Aliya Norton Soobin Seo Zhiyi Yao Wade G. Regehr |
| author_sort | Joon-Hyuk Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cb8e78a7a4b2430bac9fcfa5a63e1b30 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cb8e78a7a4b2430bac9fcfa5a63e1b302025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61190-6Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviorsJoon-Hyuk Lee0Chong Guo1Shuting Wu2Aliya Norton3Soobin Seo4Zhiyi Yao5Wade G. Regehr6Department of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41467-025-61190-6 |
| spellingShingle | Joon-Hyuk Lee Chong Guo Shuting Wu Aliya Norton Soobin Seo Zhiyi Yao Wade G. Regehr Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors Nature Communications |
| title | Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors |
| title_full | Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors |
| title_fullStr | Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors |
| title_full_unstemmed | Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors |
| title_short | Processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar-dependent behaviors |
| title_sort | processing reliant on granule cells is essential for motor learning but dispensable for social preference and numerous other cerebellar dependent behaviors |
| url | https://doi.org/10.1038/s41467-025-61190-6 |
| work_keys_str_mv | AT joonhyuklee processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT chongguo processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT shutingwu processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT aliyanorton processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT soobinseo processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT zhiyiyao processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors AT wadegregehr processingreliantongranulecellsisessentialformotorlearningbutdispensableforsocialpreferenceandnumerousothercerebellardependentbehaviors |