Gender specific requirement of GluR1 receptors in contextual conditioning but not spatial learning

The GluR1 subunit of the AMPA receptor is required for hippocampal-dependent memory formation, emotional learning and synaptic plasticity. Recent work has shown that GluR1-independent synaptic plasticity is mediated by nitric oxide. Nitric oxide activity is influenced by estrogen. It is unknown whether this gender-dependent effect conveys a gender dimorphic requirement of GluR1 for learning. This hypothesis was tested in two behavioral paradigms. In Experiment 1, the retention of contextual fear conditioning was impaired in male but not female GluR1 knockout mice. In Experiment 2, GluR1 knockout mice made significantly more arm entry errors during acquisition of a radial-arm watermaze task. This deficit was independent of gender. These results indicate that some forms of learning are gender dimorphic in GluR1 knockout mice. The results are discussed with reference to task and gender-specific interactions between GluR1 receptor intracellular signalling pathways.

► Contextual fear conditioning is disrupted in GluR1 knockout mice.
► The retention of fear memory is absent in male but not female GluR1 knockout mice.
► Spatial working memory is disrupted in GluR1 knockout mice of both genders.
► Spatial reference memory can form in the absence of GluR1.
► Spatial reference memory retention is not separable by gender.