title: In vivo synaptic scaling is mediated by GluA2-lacking AMPA receptors in the embryonic spinal cord.
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. Although 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 receptors (CP-AMPARs), whereas 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 represents similar phenomena, supporting the idea that activity blockade triggers scaling by reducing GABAA transmission.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Garcia-Bereguiain
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez-Islas
authors.forename: Casie
authors.initials: C
authors.lastname: Lindsly
authors.forename: Ellie
authors.initials: E
authors.lastname: Butler
authors.forename: Atlantis Wilkins
authors.initials: AW
authors.lastname: Hill
authors.forename: Peter
authors.initials: P
authors.lastname: Wenner
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D002642:Chick Embryo; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D009046:Motor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000172:deficiency*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011724:Pyridazines; D018091:Receptors, AMPA; D013779:Tetrodotoxin; D008012:Lidocaine; C049853:gabazine; C104722:glutamate receptor ionotropic, AMPA 2