title: Regulation of synaptic stability by AMPA receptor reverse signaling.
abstract: 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.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Ripley
authors.forename: Stefanie
authors.initials: S
authors.lastname: Otto
authors.forename: Katie
authors.initials: K
authors.lastname: Tiglio
authors.forename: Megan E
authors.initials: ME
authors.lastname: Williams
authors.forename: Anirvan
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002460:Cell Line; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D007150:Immunohistochemistry; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C093438:neuroligin 1; C104722:glutamate receptor ionotropic, AMPA 2