Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking.
Emotion enhances our ability to form vivid memories of even trivial events. Norepinephrine (NE), a neuromodulator released during emotional arousal, plays a central role in the emotional regulation of memory. However, the underlying molecular mechanism remains elusive. Toward this aim, we have examined the role of NE in contextual memory formation and in the synaptic delivery of GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)-type glutamate receptors during long-term potentiation (LTP), a candidate synaptic mechanism for learning. We found that NE, as well as emotional stress, induces phosphorylation of GluR1 at sites critical for its synaptic delivery. Phosphorylation at these sites is necessary and sufficient to lower the threshold for GluR1 synaptic incorporation during LTP. In behavioral experiments, NE can lower the threshold for memory formation in wild-type mice but not in mice carrying mutations in the GluR1 phosphorylation sites. Our results indicate that NE-driven phosphorylation of GluR1 facilitates the synaptic delivery of GluR1-containing AMPARs, lowering the threshold for LTP, thereby providing a molecular mechanism for how emotion enhances learning and memory.
Hu
Hailan
H
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Real
Eleonore
E
Takamiya
Kogo
K
Kang
Myoung-Goo
MG
Ledoux
Joseph
J
Huganir
Richard L
RL
Malinow
Roberto
R
D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D009638:Norepinephrine; D018091:Receptors, AMPA