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• W2894920963 abstract "Key points This study characterizes the mechanisms underlying defects in synaptic transmission when dynamin-related protein 1 (DRP1) is genetically eliminated. Viral-mediated knockout of DRP1 from the presynaptic terminal at the mouse calyx of Held increased initial release probability, reduced the size of the synaptic vesicle recycling pool and impaired synaptic vesicle recycling. Transmission defects could be partially restored by increasing the intracellular calcium buffering capacity with EGTA-AM, implying close coupling of Ca2+ channels to synaptic vesicles was compromised. Acute restoration of ATP to physiological levels in the presynaptic terminal did not reverse the synaptic defects. Loss of DRP1 impairs mitochondrial morphology in the presynaptic terminal, which in turn seems to arrest synaptic maturation. Abstract Impaired mitochondrial biogenesis and function is implicated in many neurodegenerative diseases, and likely affects synaptic neurotransmission prior to cellular loss. Dynamin-related protein 1 (DRP1) is essential for mitochondrial fission and is disrupted in neurodegenerative disease. In this study, we used the mouse calyx of Held synapse as a model to investigate the impact of presynaptic DRP1 loss on synaptic vesicle (SV) recycling and sustained neurotransmission. In vivo viral expression of Cre recombinase in ventral cochlear neurons of floxed-DRP1 mice generated a presynaptic-specific DRP1 knockout (DRP1-preKO), where the innervated postsynaptic cell was unperturbed. Confocal reconstruction of the calyx terminal suggested SV clusters and mitochondrial content were disrupted, and presynaptic terminal volume was decreased. Using postsynaptic voltage-clamp recordings, we found that DRP1-preKO synapses had larger evoked responses at low frequency stimulation. DRP1-preKO synapses also had profoundly altered short-term plasticity, due to defects in SV recycling. Readily releasable pool size, estimated with high-frequency trains, was dramatically reduced in DRP1-preKO synapses, suggesting an important role for DRP1 in maintenance of release-competent SVs at the presynaptic terminal. Presynaptic Ca2+ accumulation in the terminal was also enhanced in DRP1-preKO synapses. Synaptic transmission defects could be partially rescued with EGTA-AM, indicating close coupling of Ca2+ channels to SV distance normally found in mature terminals may be compromised by DRP1-preKO. Using paired recordings of the presynaptic and postsynaptic compartments, recycling defects could not be reversed by acute dialysis of ATP into the calyx terminals. Taken together, our results implicate a requirement for mitochondrial fission to coordinate postnatal synapse maturation." @default.
• W2894920963 created "2018-10-12" @default.
• W2894920963 creator A5016136321 @default.
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• W2894920963 creator A5087259396 @default.
• W2894920963 creator A5090056491 @default.
• W2894920963 date "2018-11-10" @default.
• W2894920963 modified "2023-09-29" @default.
• W2894920963 title "Presynaptic loss of dynamin‐related protein 1 impairs synaptic vesicle release and recycling at the mouse calyx of Held" @default.
• W2894920963 cites W1487318093 @default.
• W2894920963 cites W1553390829 @default.
• W2894920963 cites W1575267250 @default.
• W2894920963 cites W1584683364 @default.
• W2894920963 cites W1601000163 @default.
• W2894920963 cites W1778293074 @default.
• W2894920963 cites W1877594537 @default.
• W2894920963 cites W1918185049 @default.
• W2894920963 cites W1967002845 @default.
• W2894920963 cites W1967646152 @default.
• W2894920963 cites W1968522541 @default.
• W2894920963 cites W1969853133 @default.
• W2894920963 cites W1974750801 @default.
• W2894920963 cites W1980879721 @default.
• W2894920963 cites W1981195606 @default.
• W2894920963 cites W1989894857 @default.
• W2894920963 cites W1990737844 @default.
• W2894920963 cites W1990740805 @default.
• W2894920963 cites W1990950863 @default.
• W2894920963 cites W2000436563 @default.
• W2894920963 cites W2005968627 @default.
• W2894920963 cites W2006999571 @default.
• W2894920963 cites W2007088406 @default.
• W2894920963 cites W2010905290 @default.
• W2894920963 cites W2015600303 @default.
• W2894920963 cites W2016193338 @default.
• W2894920963 cites W2021337708 @default.
• W2894920963 cites W2022286642 @default.
• W2894920963 cites W2026709267 @default.
• W2894920963 cites W2027195402 @default.
• W2894920963 cites W2028789389 @default.
• W2894920963 cites W2034780161 @default.
• W2894920963 cites W2038394514 @default.
• W2894920963 cites W2041258962 @default.
• W2894920963 cites W2044364924 @default.
• W2894920963 cites W2045085957 @default.
• W2894920963 cites W2048730719 @default.
• W2894920963 cites W2065786892 @default.
• W2894920963 cites W2072816770 @default.
• W2894920963 cites W2079607057 @default.
• W2894920963 cites W2087693531 @default.
• W2894920963 cites W2092617299 @default.
• W2894920963 cites W2093899869 @default.
• W2894920963 cites W2098599651 @default.
• W2894920963 cites W2099034293 @default.
• W2894920963 cites W2100664594 @default.
• W2894920963 cites W2105043890 @default.
• W2894920963 cites W2107257651 @default.
• W2894920963 cites W2110672617 @default.
• W2894920963 cites W2111642216 @default.
• W2894920963 cites W2115853389 @default.
• W2894920963 cites W2125752525 @default.
• W2894920963 cites W2126384707 @default.
• W2894920963 cites W2129696839 @default.
• W2894920963 cites W2131454864 @default.
• W2894920963 cites W2136006547 @default.
• W2894920963 cites W2143410022 @default.
• W2894920963 cites W2145527534 @default.
• W2894920963 cites W2148445103 @default.
• W2894920963 cites W2150256046 @default.
• W2894920963 cites W2152712045 @default.
• W2894920963 cites W2153456027 @default.
• W2894920963 cites W2157846298 @default.
• W2894920963 cites W2167812349 @default.
• W2894920963 cites W2218964288 @default.
• W2894920963 cites W2277318350 @default.
• W2894920963 cites W2291957660 @default.
• W2894920963 cites W2300049618 @default.
• W2894920963 cites W2323479785 @default.
• W2894920963 cites W2509137173 @default.
• W2894920963 cites W2513986326 @default.
• W2894920963 cites W2563927047 @default.
• W2894920963 cites W2578173289 @default.
• W2894920963 cites W2782677553 @default.
• W2894920963 cites W2788486909 @default.
• W2894920963 cites W2795966186 @default.
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• W2894920963 doi "https://doi.org/10.1113/jp276424" @default.
• W2894920963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6292820" @default.
• W2894920963 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30285293" @default.
• W2894920963 hasPublicationYear "2018" @default.
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