title: Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling.
abstract: Neurons adapt to long-lasting changes in network activity, both in vivo and in vitro, by adjusting their synaptic strengths to stabilize firing rates. We found that homeostatic scaling of excitatory synapses was impaired in hippocampal neurons derived from mice lacking presenilin 1 (Psen1(-/-) mice) or expressing a familial Alzheimer's disease-linked Psen1 mutation (Psen1(M146V)). These findings suggest that deficits in synaptic homeostasis may contribute to brain dysfunction in Alzheimer's disease.
authors.affiliation: Department of Physiology & Biophysics, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Kara G
authors.initials: KG
authors.lastname: Pratt
authors.forename: Eric C
authors.initials: EC
authors.lastname: Zimmerman
authors.forename: David G
authors.initials: DG
authors.lastname: Cook
authors.forename: Jane M
authors.initials: JM
authors.lastname: Sullivan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008715:Methionine / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D053764:Presenilin-1 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection; D014633:Valine / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D053764:Presenilin-1; D026941:Sodium Channel Blockers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D008715:Methionine; D051058:Oncogene Protein v-akt; D014633:Valine