Chemistry

Metaplasticity

Nonsynaptic plasticity

Glutamate receptor

Biochemistry

Receptor

Autophagy

AMPA receptor

Neuroscience

Dendritic spine

Biology

Postsynaptic density

Apoptosis

Postsynaptic potential

Cell biology

Inhibitory postsynaptic potential

Synaptic plasticity

Hippocampal formation

Excitatory postsynaptic potential

Long-term potentiation

Long-term depression

Nature Communications

The pruning of dendritic spines during development requires autophagy. This process is facilitated by long-term depression (LTD)-like mechanisms, which has led to speculation that LTD, a fundamental form of synaptic plasticity, also requires autophagy. Here, we show that the induction of LTD via activation of NMDA receptors or metabotropic glutamate receptors initiates autophagy in the postsynaptic dendrites in mice. Dendritic autophagic vesicles (AVs) act in parallel with the endocytic machinery to remove AMPA receptor subunits from the membrane for degradation. During NMDAR-LTD, key postsynaptic proteins are sequestered for autophagic degradation, as revealed by quantitative proteomic profiling of purified AVs. Pharmacological inhibition of AV biogenesis, or conditional ablation of atg5 in pyramidal neurons abolishes LTD and triggers sustained potentiation in the hippocampus. These deficits in synaptic plasticity are recapitulated by knockdown of atg5 specifically in postsynaptic pyramidal neurons in the CA1 area. Conducive to the role of synaptic plasticity in behavioral flexibility, mice with autophagy deficiency in excitatory neurons exhibit altered response in reversal learning. Therefore, local assembly of the autophagic machinery in dendrites ensures the degradation of postsynaptic components and facilitates LTD expression.

Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice