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<div><p>Amyloid precursor protein (APP)-null mice exhibit significant deficits in motor performance, including reduced grip strength and impaired locomotion; however, the underlying neurophysiological mechanisms remain unclear. In this study, we show that conditional knockdown of APP sel...
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2025
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| _version_ | 1849927642319421440 |
|---|---|
| author | Miao-Jin Ji (22676552) |
| author2 | Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| author2_role | author author author author author author author author author author author |
| author_facet | Miao-Jin Ji (22676552) Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| author_role | author |
| dc.creator.none.fl_str_mv | Miao-Jin Ji (22676552) Tong-Xuan Wu (22676555) Chenhao Tian (10801643) Xiang Cao (298023) Ruyuan Wei (22676558) Yin-Yin Yang (301866) Xinran Meng (11537536) Huanyao Tang (22676561) Tiantao Cui (22676564) Jiao Yang (623531) Xin Tang (134573) Chao Liu (43092) |
| dc.date.none.fl_str_mv | 2025-11-24T18:30:25Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pbio.3003513.s009 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/xxx_/30697262 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |
| dc.title.none.fl_str_mv | xxx. |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <div><p>Amyloid precursor protein (APP)-null mice exhibit significant deficits in motor performance, including reduced grip strength and impaired locomotion; however, the underlying neurophysiological mechanisms remain unclear. In this study, we show that conditional knockdown of APP selectively in Purkinje cells (PCs) recapitulates these motor deficits, while exogenous expression of APP in APP-null mice rescues motor function. Electrophysiological analysis revealed that APP deficiency leads to aberrant firing patterns in PCs and reduces inhibitory synaptic transmission onto neurons of the deep cerebellar nucleus (DCN). We identified a marked reduction in Nav1.6-mediated sodium currents as the key mechanism underlying abnormal action potential firing and propagation in APP-deficient PCs. Importantly, all electrophysiological and behavioral deficits were rescued by PC-specific APP reconstitution. These findings reveal a novel and essential role for APP in cerebellar motor control by regulating Nav1.6 channel activity and PC excitability.</p></div> |
| eu_rights_str_mv | openAccess |
| id | Manara_59f27b7f816f71ccc048e566181ef660 |
| identifier_str_mv | 10.1371/journal.pbio.3003513.s009 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30697262 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | xxx.Miao-Jin Ji (22676552)Tong-Xuan Wu (22676555)Chenhao Tian (10801643)Xiang Cao (298023)Ruyuan Wei (22676558)Yin-Yin Yang (301866)Xinran Meng (11537536)Huanyao Tang (22676561)Tiantao Cui (22676564)Jiao Yang (623531)Xin Tang (134573)Chao Liu (43092)BiochemistryCell BiologyMolecular BiologyNeurosciencePhysiologyDevelopmental BiologyInfectious Diseasesmediated sodium currentsdeep cerebellar nucleusaberrant firing patternsspecific app reconstitutioncerebellar motor controlapp deficiency leadselectrophysiological analysis revealed6 channel activitymotor performancemotor functionmotor deficitsapp selectivelypurkinje cellsmarked reductionimpaired locomotionfindings revealexogenous expressionessential roledcn ).conditional knockdownbehavioral deficits<div><p>Amyloid precursor protein (APP)-null mice exhibit significant deficits in motor performance, including reduced grip strength and impaired locomotion; however, the underlying neurophysiological mechanisms remain unclear. In this study, we show that conditional knockdown of APP selectively in Purkinje cells (PCs) recapitulates these motor deficits, while exogenous expression of APP in APP-null mice rescues motor function. Electrophysiological analysis revealed that APP deficiency leads to aberrant firing patterns in PCs and reduces inhibitory synaptic transmission onto neurons of the deep cerebellar nucleus (DCN). We identified a marked reduction in Nav1.6-mediated sodium currents as the key mechanism underlying abnormal action potential firing and propagation in APP-deficient PCs. Importantly, all electrophysiological and behavioral deficits were rescued by PC-specific APP reconstitution. These findings reveal a novel and essential role for APP in cerebellar motor control by regulating Nav1.6 channel activity and PC excitability.</p></div>2025-11-24T18:30:25ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pbio.3003513.s009https://figshare.com/articles/figure/xxx_/30697262CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306972622025-11-24T18:30:25Z |
| spellingShingle | xxx. Miao-Jin Ji (22676552) Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |
| status_str | publishedVersion |
| title | xxx. |
| title_full | xxx. |
| title_fullStr | xxx. |
| title_full_unstemmed | xxx. |
| title_short | xxx. |
| title_sort | xxx. |
| topic | Biochemistry Cell Biology Molecular Biology Neuroscience Physiology Developmental Biology Infectious Diseases mediated sodium currents deep cerebellar nucleus aberrant firing patterns specific app reconstitution cerebellar motor control app deficiency leads electrophysiological analysis revealed 6 channel activity motor performance motor function motor deficits app selectively purkinje cells marked reduction impaired locomotion findings reveal exogenous expression essential role dcn ). conditional knockdown behavioral deficits |