Somatic accumulation of GluA1-AMPA receptors leads to selective cognitive impairments in mice
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’...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
25 June 2018
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| In: |
Frontiers in molecular neuroscience
Year: 2018, Volume: 11 |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2018.00199 |
| Online Access: | Verlag, Volltext: https://doi.org/10.3389/fnmol.2018.00199 Verlag: https://www.frontiersin.org/articles/10.3389/fnmol.2018.00199/full 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 04.03.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2018.00199 |