AMPA receptors are exocytosed in stimulated spines and adjacent dendrites in a Ras-ERK-dependent manner during long-term potentiation.
The exocytosis of AMPA receptors is a key step in long-term potentiation (LTP), yet the timing and location of exocytosis and the signaling pathways involved in exocytosis during synaptic plasticity are not fully understood. Here we combine two-photon uncaging with two-photon imaging of a fluorescent label of surface AMPA receptors to monitor individual AMPA receptor exocytosis events near spines undergoing LTP. AMPA receptors that reached the stimulated spine came from a combination of preexisting surface receptors (70-90%) and newly exocytosed receptors (10-30%). We observed exocytosis in both the dendrite and spine under basal conditions. The rate of AMPA receptor exocytosis increased approximately 5-fold during LTP induction and decayed to the basal level within approximately 1 min, both in the stimulated spine and in the dendrite within approximately 3 microm of the stimulated spine. AMPA receptors inserted in the spine were trapped in the spine in an activity-dependent manner. The activity-dependent exocytosis required the Ras-ERK pathway, but not CaMKII. Thus, diffusive Ras-ERK signaling presumably serves as an important means for signaling from synapses to dendritic shafts to recruit AMPA receptors into synapses during LTP.
Patterson
Michael A
MA
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Szatmari
Erzsebet M
EM
Yasuda
Ryohei
R
D000818:Animals; D005089:Exocytosis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005456:Fluorescent Dyes; D007700:Kinetics; D017774:Long-Term Potentiation; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D005456:Fluorescent Dyes; D018091:Receptors, AMPA; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins