Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice - Aix-Marseille Université Access content directly
Journal Articles Frontiers in Molecular Neuroscience Year : 2018

Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice

David Bannerman
  • Function : Author
Thilo Borchardt
  • Function : Author
Vidar Jensen
  • Function : Author
Andrey Rozov
  • Function : Author
Nadia N Haj-Yasein
  • Function : Author
Daniel Zamanillo
  • Function : Author
Thorsten Bus
  • Function : Author
Isabel Grube
  • Function : Author
Giselind Adelmann
  • Function : Author
Rolf Sprengel
  • Function : Author

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 (Gria1 R/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 Gria1 R/R mice. These immunohistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (short-term and long-term potentiation, STP and LTP, respectively) 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 Gria1 R/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.
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hal-01963842 , version 1 (21-12-2018)

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David Bannerman, Thilo Borchardt, Vidar Jensen, Andrey Rozov, Nadia N Haj-Yasein, et al.. Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice. Frontiers in Molecular Neuroscience, 2018, 11, ⟨10.3389/fnmol.2018.00199⟩. ⟨hal-01963842⟩

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