Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.

Autor:	Cheng X; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA., Tang Y; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA., Vidyadhara DJ; Department of Neurology, Yale University, CT, USA.; Department of Neuroscience, Yale University, CT, USA., Li BZ; Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Department of Electrical Engineering, University of Colorado, Denver, Denver, CO, USA., Zimmerman M; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA.; Department of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA., Pak A; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA., Nareddula S; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA., Edens PA; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA., Chandra SS; Department of Neurology, Yale University, CT, USA.; Department of Neuroscience, Yale University, CT, USA.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, CT, USA., Chubykin AA; Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Sep 06; Vol. 26 (10), pp. 107842. Date of Electronic Publication: 2023 Sep 06 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.107842
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2023 The Authors.)
Databáze:	MEDLINE
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