| First Author | Cheng X | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 10 | Pages | 107842 |
| PubMed ID | 37766983 | Mgi Jnum | J:341938 |
| Mgi Id | MGI:7538589 | Doi | 10.1016/j.isci.2023.107842 |
| Citation | Cheng X, et al. (2023) Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice. iScience 26(10):107842 |
| abstractText | Auxilin (DNAJC6/PARK19), an endocytic co-chaperone, is essential for maintaining homeostasis in the readily releasable pool (RRP) by aiding clathrin-mediated uncoating of synaptic vesicles. Its loss-of-function mutations, observed in familial Parkinson's disease (PD), lead to basal ganglia motor deficits and cortical dysfunction. We discovered that auxilin-knockout (Aux-KO) mice exhibited impaired pre-synaptic plasticity in layer 4 to layer 2/3 pyramidal cell synapses in the primary visual cortex (V1), including reduced short-term facilitation and depression. Computational modeling revealed increased RRP refilling during short repetitive stimulation, which diminished during prolonged stimulation. Silicon probe recordings in V1 of Aux-KO mice demonstrated disrupted visual cortical circuit responses, including reduced orientation selectivity, compromised visual mismatch negativity, and shorter visual familiarity-evoked theta oscillations. Pupillometry analysis revealed an impaired optokinetic response. Auxilin-dependent pre-synaptic endocytosis dysfunction was associated with deficits in pre-synaptic plasticity, visual cortical functions, and eye movement prodromally or at the early stage of motor symptoms. |
