Somatic accumulation of GluA1-AMPA receptors leads to selective cognitive impairments in mice

• Verfasst von: Bannerman, David [VerfasserIn]
• Verfasst von: Rozov, Andrei [VerfasserIn]
• Verfasst von: Sprengel, Rolf [VerfasserIn]
• Titel: Somatic accumulation of GluA1-AMPA receptors leads to selective cognitive impairments in mice
• Verf.angabe: David M. Bannerman, Thilo Borchardt, Vidar Jensen, Andrey Rozov, Nadia N. Haj-Yasein, Nail Burnashev, Daniel Zamanillo, Thorsten Bus, Isabel Grube, Giselind Adelmann, J. Nicholas P. Rawlins and Rolf Sprengel
• E-Jahr: 2018
• Jahr: 25 June 2018
• Umfang: 14 S.
• Fussnoten: Gesehen am 04.03.2020
• Titel Quelle: Enthalten in: Frontiers in molecular neuroscience
• Ort Quelle: Lausanne : Frontiers Research Foundation, 2008
• Jahr Quelle: 2018
• Band/Heft Quelle: 11(2018) Artikel-Nummer 199, 14 Seiten
• ISSN Quelle: 1662-5099
• DOI: doi:10.3389/fnmol.2018.00199
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AMPA receptors
• Sach-SW: GluA1
• Sach-SW: Long-Term Potentiation
• Sach-SW: Morris water-maze
• Sach-SW: RNA-editing
• Sach-SW: spatial memory
• Sach-SW: spatial working memory
• K10plus-PPN: 1691521817

Abstract

The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the ‘trafficking compromised’ GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult Gria1R/R mice. These immunhistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (STP and LTP) in the CA1 subfield following tetanic and theta-burst stimulation. Nevertheless, spatial reference memory acquisition in the Morris water-maze and on an appetitive Y-maze task was unaffected in Gria1R/R mice. In contrast, spatial working/short-term memory during both spontaneous and rewarded alternation tasks was dramatically impaired. These findings identify the GluA1(Q600R) mutation as a loss of function mutation that provides independent evidence for the selective role of GluA1 in the expression of short-term memory.