Neuron
Volume 83, Issue 2, 16 July 2014, Pages 417-430
Journal home page for Neuron

Article
ATP P2X Receptors Downregulate AMPA Receptor Trafficking and Postsynaptic Efficacy in Hippocampal Neurons

https://doi.org/10.1016/j.neuron.2014.06.005Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Activation of P2XRs by ATP or glial-derived ATP decreases synaptic strength

  • P2XRs promote clathrin-mediated endocytosis of AMPAR

  • P2XR activation reduces surface AMPAR in dendrites and at synapses

  • P2X-mediated AMPAR inhibition requires calcium and phosphatase or CamKII activities

Summary

P2X receptors (P2XRs) are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons or glia. Although purinergic signaling has multiple effects on synaptic transmission and plasticity, P2XR function at brain synapses remains to be established. Here, we show that activation of postsynaptic P2XRs by exogenous ATP or noradrenaline-dependent glial release of endogenous ATP decreases the amplitude of miniature excitatory postsynaptic currents and AMPA-evoked currents in cultured hippocampal neurons. We also observed a P2X-mediated depression of field potentials recorded in CA1 region from brain slices. P2X2Rs trigger dynamin-dependent internalization of AMPA receptors (AMPARs), leading to reduced surface AMPARs in dendrites and at synapses. AMPAR alteration required calcium influx through opened ATP-gated channels and phosphatase or CamKII activities. These findings indicate that postsynaptic P2XRs play a critical role in regulating the surface expression of AMPARs and thereby regulate the synaptic strength.

Cited by (0)

5

Co-first author