AUTHOR=Bannerman David M. , Borchardt Thilo , Jensen Vidar , Rozov Andrey , Haj-Yasein Nadia N. , Burnashev Nail , Zamanillo Daniel , Bus Thorsten , Grube Isabel , Adelmann Giselind , Rawlins J. Nicholas P. , Sprengel Rolf 

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

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=11

YEAR=2018

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2018.00199

DOI=10.3389/fnmol.2018.00199

ISSN=1662-5099

ABSTRACT=<p>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 (<italic>Gria1<sup>R/R</sup></italic>), 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 <italic>Gria1<sup>R/R</sup></italic> 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 <italic>Gria1<sup>R/R</sup></italic> 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.</p>