title: Homeostatic scaling requires group I mGluR activation mediated by Homer1a.
abstract: Homeostatic scaling is a non-Hebbian form of neural plasticity that maintains neuronal excitability and informational content of synaptic arrays in the face of changes of network activity. Here, we demonstrate that homeostatic scaling is dependent on group I metabotropic glutamate receptor activation that is mediated by the immediate early gene Homer1a. Homer1a is transiently upregulated during increases in network activity and evokes agonist-independent signaling of group I mGluRs that scales down the expression of synaptic AMPA receptors. Homer1a effects are dynamic and play a role in the induction of scaling. Similar to mGluR-LTD, Homer1a-dependent scaling involves a reduction of tyrosine phosphorylation of GluA2 (GluR2), but is distinct in that it exploits a unique signaling property of group I mGluR to confer cell-wide, agonist-independent activation of the receptor. These studies reveal an elegant interplay of mechanisms that underlie Hebbian and non-Hebbian plasticity.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Hu
authors.forename: Joo Min
authors.initials: JM
authors.lastname: Park
authors.forename: Sungjin
authors.initials: S
authors.lastname: Park
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Marlin H
authors.initials: MH
authors.lastname: Dehoff
authors.forename: Sangmok
authors.initials: S
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schwarz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: David J
authors.initials: DJ
authors.lastname: Linden
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1