In vivo synaptic scaling is mediated by GluA2-lacking AMPA receptors in the embryonic spinal cord

• Type of Material: Article
• Authors: Miguel Angel Garcia-Bereguiain, Emory University; Carlos E Gonzalez Islas, Emory University; Casie Lindsly, Emory University; Ellie Butler, Emory University; Atlantis Wilkins Hill, Emory University; Peter Wenner, Emory University
• Language: English
• Date: 2013-04-17
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 the authors
• Final Published Version (URL): http://www.jneurosci.org/content/33/16/6791.long
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 33
• Issue: 16
• Start Page: 6791
• End Page: 6799
• Grant/Funding Information: This research was supported by Grants from the National Institute of Neurological Disorders and Stroke, the Whitehall Foundation, and the Neilsen Foundation to P. Wenner. Miguel Angel Garcia Bereguiain was sponsored by a fellowship from Rafael del Pino Foundation.
• Research Categories: Biology, Neuroscience; Biology, Physiology

Abstract

When spiking activity within a network is perturbed for hours to days, compensatory changes in synaptic strength are triggered that are thought to be important for the homeostatic maintenance of network or cellular spiking activity. In one form of this homeostatic plasticity, called synaptic scaling, all of a cell’s AMPAergic miniature postsynaptic currents (mEPSCs) are increased or decreased by some scaling factor. While synaptic scaling has been observed in a variety of systems, the mechanisms that underlie AMPAergic scaling have been controversial. Certain studies find that synaptic scaling is mediated by GluA2-lacking calcium permeable receptors (CP-AMPARs), while others have found that scaling is mediated by GluA2-containing calcium impermeable receptors (CI-AMPARs). Spontaneous network activity is observed in most developing circuits, and in the spinal cord this activity drives embryonic movements. Blocking spontaneous network activity in the chick embryo by infusing lidocaine in vivo triggers synaptic scaling in spinal motoneurons; here we show that AMPAergic scaling occurs through increases in mEPSC conductance that appear to be mediated by the insertion of GluA2-lacking AMPA receptors at the expense of GluA2-containing receptors. We have previously reported that in vivo blockade of GABAA transmission, at a developmental stage when GABA is excitatory, also triggered AMPAergic synaptic scaling. Here, we show that this form of AMPAergic scaling is also mediated by CP-AMPARs. These findings suggest that AMPAergic scaling triggered by blocking spiking activity or GABAA receptor transmission represent similar phenomenon, supporting the idea that activity-blockade triggers scaling by reducing GABAA transmission.