Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity.
BACKGROUND
Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP.


RESULTS
We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism.


CONCLUSIONS
These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation.
Lüthi
Andreas
A
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol, BS8 1TD, UK. Andreas.Luthi@fmi.ch <Andreas.Luthi@fmi.ch>
Wikström
Martin A
MA
Palmer
Mary J
MJ
Matthews
Paul
P
Benke
Tim A
TA
Isaac
John T R
JT
Collingridge
Graham L
GL
D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate