title: Overexpression of STIM1 in neurons in mouse brain improves contextual learning and impairs long-term depression.
abstract: STIM1 is an endoplasmic reticulum calcium sensor that is involved in several processes in neurons, including store-operated calcium entry. STIM1 also inhibits voltage-gated calcium channels, such as Cav1.2 and Cav3.1, and is thus considered a multifunctional protein. The aim of this work was to investigate the ways in which transgenic neuronal overexpression of STIM1 in FVB/NJ mice affects animal behavior and the electrophysiological properties of neurons in acute hippocampal slices. We overexpressed STIM1 from the Thy1.2 promoter and verified neuronal expression by quantitative reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry. Mature primary hippocampal cultures expressed STIM1 but exhibited no changes in calcium homeostasis. Basal synaptic transmission efficiency and short-term plasticity were comparable in slices that were isolated from transgenic mice, similarly as the magnitude of long-term potentiation. However, long-term depression that was induced by the glutamate receptor 1/5 agonist (S)-3,5-dihydroxyphenylglycine was impaired in STIM1 slices. Interestingly, transgenic mice exhibited a decrease in anxiety-like behavior and improvements in contextual learning. In summary, our data indicate that STIM1 overexpression in neurons in the brain perturbs metabotropic glutamate receptor signaling, leading to impairments in long-term depression and alterations in animal behavior. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., 02-109 Warsaw, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Majewski
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., 02-109 Warsaw, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Maciąg
authors.affiliation: Laboratory of Animal Models, Neurobiology Centre, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Paweł M
authors.initials: PM
authors.lastname: Boguszewski
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., 02-109 Warsaw, Poland.
authors.forename: Iga
authors.initials: I
authors.lastname: Wasilewska
authors.affiliation: Laboratory of Neuroscience, Dept. Biophysics, Wroclaw Medical University, 3a Chalubinskiego Str., 50-368 Wroclaw, Poland; Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, 30 Cybulskiego Str., 50-205 Wroclaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wiera
authors.affiliation: Laboratory of Neuroscience, Dept. Biophysics, Wroclaw Medical University, 3a Chalubinskiego Str., 50-368 Wroclaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wójtowicz
authors.affiliation: Laboratory of Neuroscience, Dept. Biophysics, Wroclaw Medical University, 3a Chalubinskiego Str., 50-368 Wroclaw, Poland; Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, 30 Cybulskiego Str., 50-205 Wroclaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Mozrzymas
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena Str., 02-109 Warsaw, Poland. Electronic address: jacek.kuznicki@iimcb.gov.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuznicki
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D007858:Learning; D036881:Long-Term Synaptic Depression; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism*
chemical_list: C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1
keywords: Behavior; LTD; ORAIs; SOCE; STIMs; mGluR