Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 1, Pages 367-372Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1015163108
Keywords
GluR2 N-terminal domain; Presynaptic stabilization; Presynaptic input dynamics
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Funding
- National Institutes of Health [NS052772, NS064124]
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The establishment of neuronal circuits relies on the stabilization of functionally appropriate connections and the elimination of inappropriate ones. Here we report that postsynaptic AMPA receptors play a critical role in regulating the stability of glutamatergic synapses. Removal of surface AMPA receptors leads to a decrease in the number and stability of excitatory presynaptic inputs, whereas overexpression increases synapse number and stability. Furthermore, overexpression of AMPA receptors along with Neuroligin-1 in 293T cells is sufficient to stabilize presynaptic inputs from cortical neurons onto heterologous cells. The stabilization of presynaptic inputs by AMPA receptors is not dependent on receptor-mediated current and instead relies on structural interactions mediated by the N-terminal domain of the glutamate receptor 2 (GluR2) subunit. These observations indicate that transsynaptic signaling mediated by the extracellular domain of GluR2 regulates the stability of presynaptic terminals.
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