ATP hydrolysis is required for the rapid regulation of AMPA receptors during basal synaptic transmission and long-term synaptic plasticity.
ATP hydrolysis is critical for many cellular processes; however, the acute requirement for ATP hydrolysis in synaptic transmission and plasticity in neurons is unknown. Here we studied the effects of postsynaptically applying the non-hydrolyzable ATP analogue adenosine 5'-[beta,gamma-methylene]triphosphate (AMP-PCP) into hippocampal CA1 pyramidal cells in hippocampal slices. The effects of this manipulation were investigated on basal transmission and on two forms of long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD). AMP-PCP caused an increase in basal AMPA receptor (AMPAR)-mediated transmission, which occurred rapidly within minutes of infusing the drug. This effect was selective for AMPARs, since pharmacologically isolated NMDAR-mediated synaptic currents did not exhibit this run up. In two-pathway experiments infusion of AMP-PCP blocked the induction of both LTD and LTP. These findings show an acute and selective role for ATP hydrolysis in regulating AMPAR function both during basal transmission and long-term synaptic plasticity. Recent evidence indicates that AMPARs are selectively and acutely regulated by the ATPase N-ethylmaleimide-sensitive factor (NSF), which forms part of a multi-protein complex with AMPARs. Our data are consistent with the idea that such a mechanism that can acutely bi-directionally regulate AMPAR function at synapses and requires ATP hydrolysis is necessary for rapid activity-dependent changes in synaptic strength.
Lim
Wonil
W
Department of Anatomy, MRC Centre for Synaptic Plasticity, University of Bristol, Bristol BS8 1TD, UK.
Isaac
John T R
JT
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006868:Hydrolysis; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018091:Receptors, AMPA; D000255:Adenosine Triphosphate