Activity- or experience-dependent plasticity has been associated with the trafficking of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) in a number of experimental systems. In some cases it has been shown that CP-AMPARs are only transiently present and can be removed in an activity-dependent manner. Here we test the hypothesis that the presence of CP-AMPARs confers instability onto recently potentiated synapses. Previously we have shown that altered sensory input (single-whisker experience; SWE) strengthens layer 4-2/3 excitatory synapses in mouse primary somatosensory cortex, in part by the trafficking of CP-AMPARs. Both in vivo and in vitro, this potentiation is labile, and can be depressed by N-Methyl-D-aspartate receptor (NMDAR)-activation. In the present study, the role of CP-AMPARs in conferring this synaptic instability after in vivo potentiation was evaluated. We develop an assay to depress the strength of individual layer 4-2/3 excitatory synapses after SWE, using a strontium (Sr++)-replaced artificial cerebrospinal fluid (ACSF) solution (Sr-depression). This method allows disambiguation of changes in quantal amplitude (a post-synaptic measure) from changes in event frequency (typically a presynaptic phenomenon). Presynaptic stimulation paired with post-synaptic depolarization in Sr++ lead to a rapid and significant reduction in EPSC amplitude with no change in event frequency. Sr-depression at recently potentiated synapses required NMDARs, but could still occur when CP-AMPARs were not present. As a further dissociation between the presence of CP-AMPARs and Sr-depression, CP-AMPARs could be detected in some cells from control, whisker-intact animals, although Sr-depression was never observed. Taken together, our findings suggest that CP-AMPARs are neither sufficient nor necessary for synaptic depression after in vivo plasticity in somatosensory cortex. This article is part of a Special Issue entitled “Calcium permeable AMPARs in synaptic plasticity and disease.”
Keywords: metaplasticity, NASPM, philanthotoxin, depotentiation, rectification, neocortex, development, critical period
Citation: Wen JA and Barth AL (2012) Synaptic lability after experience-dependent plasticity is not mediated by calcium-permeable AMPARs. Front. Mol. Neurosci. 5:15. doi: 10.3389/fnmol.2012.00015
Received: 13 October 2011; Accepted: 01 February 2012;
Published online: 29 February 2012.
Edited by:R. Suzanne Zukin, Albert Einstein College of Medicine, USA
Reviewed by:Hey-Kyoung Lee, Johns Hopkins University, USA
Copyright: © 2012 Wen and Barth. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Alison L. Barth, Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213, USA. e-mail: email@example.com