Local biogenesis of autophagic vesicles in neuronal dendrites facilitates long-term synaptic depression

ABSTRACT

Neurons are highly polarized and functionally compartmentalized cells. Under basal conditions, the biogenesis of autophagic vesicles (AVs) was previously shown to take place in the axon tip. As the sequestration of autophagic cargo occurs during the formation of nascent AVs, this would mean that only axonal proteins can be degraded via macroautophagy/autophagy, unless AV biogenesis can also take place on demand, in other neuronal compartments. Our work shows that indeed, activation of NMDA or group I metabotropic glutamate receptors during long-term synaptic depression (LTD) triggers the biogenesis of AVs locally in dendrites. Under these conditions, nascent dendritic AVs are required for synaptic plasticity, as they sequester postsynaptic proteins, whose removal from the postsynapse is necessary for LTD.

KEYWORDS:

• Atg5
• autophagic vesicle biogenesis
• cognitive flexibility
• dendrites
• excitatory neurons
• hippocampus
• synaptic plasticity
• ULK1 complex

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by an ERC starting grant to V.N. (NEUROPHAGY, grant number:714983)