| First Author | Bannerman DM | Year | 2018 |
| Journal | Front Mol Neurosci | Volume | 11 |
| Pages | 199 | PubMed ID | 29988555 |
| Mgi Jnum | J:277358 | Mgi Id | MGI:6330917 |
| Doi | 10.3389/fnmol.2018.00199 | Citation | Bannerman DM, et al. (2018) Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice. Front Mol Neurosci 11:199 |
| abstractText | The GluA1 subunit of the L-alpha-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. |
