Long-term synaptic depression triggers local biogenesis of autophagic vesicles in dendrites and requires autophagic degradation

biorxiv(2020)

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摘要
In neurons, biogenesis of autophagic vesicles (AVs) is spatially confined to the axon tip under baseline conditions. However, it remains unknown whether their biogenesis can be induced in other neuronal compartments following synaptic activity in order to serve local functions. Here, we show that both major types of long-term synaptic depression (LTD), a form of plasticity expressed by the shrinkage and elimination of dendritic spines, trigger the rapid and local biogenesis of AVs in post-synaptic dendrites. In return, autophagy is indispensable for LTD, as either genetic ablation of in pyramidal neurons or acute pharmacological inhibition of AV biogenesis totally prevents LTD induction. Using quantitative proteomic profiling of purified AVs, we reveal that upon LTD the autophagic cargo is significantly enriched for synaptic proteins, as well as modulators of the actin cytoskeleton and autism-implicated proteins. In line with these findings, a mild autophagy deficit is sufficient to impair behavioral flexibility, a cognitive function that requires efficient LTD. Therefore, local synthesis and assembly of the autophagic machinery in dendrites ensure the elimination of synaptic structures via degradation of their components, facilitating plasticity and associated behaviors.
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关键词
autophagic vesicles,synaptic depression,dendrites,long-term
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