title: Postsynaptic expression of homeostatic plasticity at neocortical synapses.
abstract: Synaptic scaling is a form of homeostatic plasticity that scales synaptic strengths up or down to compensate for prolonged changes in activity. It has been controversial whether this plasticity is expressed presynaptically, postsynaptically, or both. Here we describe in detail the homeostatic changes that take place at excitatory synapses in visual cortical cultures after 1 or 2 d of activity blockade. After 7-10 d in vitro, activity blockade significantly increased postsynaptic accumulation of synaptic AMPA receptors via proportional increases in glutamate receptor 1 (GluR1) and GluR2. Time-lapse imaging of enhanced green fluorescent protein-tagged AMPA receptors revealed that receptor accumulation increased progressively over 2 d of activity blockade and affected the entire population of imaged synapses. The strength of synaptic connections between pyramidal neurons was more than doubled after activity blockade without affecting short-term depression or the coefficient of variation of the postsynaptic responses. Furthermore, uptake of the fluorescent styryl dye FM1-43 (N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl] pyridinium dibromide) by presynaptic terminals was not different at control and activity-blocked synapses. In addition to the increased accumulation of postsynaptic AMPA receptors, boosting of dendritic AMPA currents by sodium channels was increased by activity blockade. These data indicate that, at young neocortical synapses, synaptic scaling has a predominantly postsynaptic locus and functions as a gain control mechanism to regulate neuronal activity without affecting the dynamics of synaptic transmission.
authors.affiliation: Department of Biology and Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
authors.forename: Corette J
authors.initials: CJ
authors.lastname: Wierenga
authors.forename: Keiji
authors.initials: K
authors.lastname: Ibata
authors.forename: Gina G
authors.initials: GG
authors.lastname: Turrigiano
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation / Q000379:methods; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D019579:Neocortex / Q000166:cytology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine; D008565:Membrane Proteins; D011189:Potassium Chloride; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D016704:Synapsins; D013779:Tetrodotoxin; D016875:tau Proteins; C501449:Dlg4 protein, rat; C073804:FM1 43; C013411:biocytin; C104722:glutamate receptor ionotropic, AMPA 2