Reference - Detail
| RRC ID | 83936 |
|---|---|
| Author | Wu XM, Lu B, He JY, Zhang YX, Wu ZY, Xiong ZQ. |
| Title | Aberrant outputs of glutamatergic neurons in deep cerebellar nuclei mediate dystonic movements. |
| Journal | Sci Adv |
| Abstract |
Dystonia, characterized by repetitive twisting movements or abnormal postures, has been linked to the deep cerebellar nuclei (DCN). However, the specific roles of distinct neuronal populations within the DCN in driving dystonic behaviors remain unclear. This study explores the contributions of three distinct groups of DCN neurons in an animal model of paroxysmal dystonia harboring a mutation in the proline-rich transmembrane protein 2 (Prrt2) gene. We observed sustained calcium activity elevation across glutamatergic, glycinergic, and GABAergic inferior olive (IO)-projecting neurons within the DCN during episodes of dystonia in Prrt2-mutant mice. However, only the optogenetic activation of DCN glutamatergic neurons, but not glycinergic or GABAergic IO-projecting neurons, elicited dystonia-like behaviors in normal mice. Selective ablation of DCN glutamatergic neurons effectively eliminated aberrant cerebellar DCN outputs and alleviated dystonia attacks in both Prrt2-associated and kainic acid-induced dystonia mouse models. Collectively, our findings highlight the pivotal role of aberrant activation of DCN glutamatergic neurons in the neuropathological mechanisms underlying cerebellar-originated dystonia. |
| Volume | 11(19) |
| Pages | eadp2377 |
| Published | 2025-5-9 |
| DOI | 10.1126/sciadv.adp2377 |
| PMID | 40344058 |
| PMC | PMC12063653 |
| MeSH | Animals Cerebellar Nuclei* / metabolism Cerebellar Nuclei* / pathology Cerebellar Nuclei* / physiopathology Disease Models, Animal Dystonia* / metabolism Dystonia* / physiopathology Dystonic Disorders* / metabolism Dystonic Disorders* / physiopathology Glutamic Acid* / metabolism Male Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mutation Neurons* / metabolism Neurons* / pathology |
| IF | 13.117 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC10109 |