title: Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain.
abstract: AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process. This highly sequence-diverse domain mediates synaptic anchoring in a subunit-selective manner. Receptors lacking the NTD exhibit increased mobility in synapses, depress synaptic transmission and are unable to sustain long-term potentiation (LTP). Thus, synaptic transmission and the expression of LTP are dependent upon an AMPAR anchoring mechanism that is driven by the NTD.
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Jake F
authors.identifier: 0000-0002-8698-3823
authors.initials: JF
authors.lastname: Watson
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Hinze
authors.initials: H
authors.lastname: Ho
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Ingo H
authors.identifier: 0000-0002-7291-2581
authors.initials: IH
authors.lastname: Greger
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D018091:Receptors, AMPA
keywords: AMPA receptor; LTP; N-terminal domain; NTD; mouse; neuroscience; synapse