GluR1 links structural and functional plasticity at excitatory synapses.
Long-term potentiation (LTP), a cellular model of learning and memory, produces both an enhancement of synaptic function and an increase in the size of the associated dendritic spine. Synaptic insertion of AMPA receptors is known to play an important role in mediating the increase in synaptic strength during LTP, whereas the role of AMPA receptor trafficking in structural changes remains unexplored. Here, we examine how the cell maintains the correlation between spine size and synapse strength during LTP. We found that cells exploit an elegant solution by linking both processes to a single molecule: the AMPA-type glutamate receptor subunit 1 (GluR1). Synaptic insertion of GluR1 is required to permit a stable increase in spine size, both in hippocampal slice cultures and in vivo. Synaptic insertion of GluR1 is not sufficient to drive structural plasticity. Although crucial to the expression of LTP, the ion channel function of GluR1 is not required for the LTP-driven spine size enhancement. Remarkably, a recombinant cytosolic C-terminal fragment (C-tail) of GluR1 is driven to the postsynaptic density after an LTP stimulus, and the synaptic incorporation of this isolated GluR1 C-tail is sufficient to permit spine enlargement even when postsynaptic exocytosis of endogenous GluR1 is blocked. We conclude that during plasticity, synaptic insertion of GluR1 has two functions: the established role of increasing synaptic strength via its ligand-gated ion channel, and a novel role through the structurally stabilizing effect of its C terminus that permits an increase in spine size.
Kopec
Charles D
CD
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Real
Eleonore
E
Kessels
Helmut W
HW
Malinow
Roberto
R
D000818:Animals; D049229:Dendritic Spines / Q000502:physiology; D018014:Gene Transfer Techniques; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000502:physiology*; D012845:Sindbis Virus / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D018091:Receptors, AMPA