The GRIA1 AMPA receptor subunit and selective learning

Abstract

The GRIA1 subunit of the AMPA receptor, encoded by the GRIA1 gene, has been implicated in schizophrenia. Schizophrenia is associated with impairments in attention that may lead to other symptoms due to a failure to learn selectively (e.g., learning about redundant cues). In mice, gene-targeted inactivation of GRIA1 impairs hippocampal synaptic plasticity and alters learning and memory. To test the role of GRIA1 in selective learning, we trained mice lacking GRIA1 on the blocking procedure. GRIA1 knockout mice showed normal blocking of appetitive Pavlovian conditioning, in which prior learning of an auditory cue reduced subsequent acquisition of conditioned responding to a visual cue when the two cues were trained in compound. GRIA1 knockout mice, however, failed to show blocking of flavour preference conditioning despite normal learning of the flavour that, in contrast, was effective in blocking conditioning in control mice. This impairment occurred under conditions in which mice were exposed to one flavour a day and when exposed to two flavours a day to aid discrimination between flavours. The dissociation between learning with visual cues and learning with flavours may suggest that GRIA1 containing AMPA receptors are necessary for selective learning for particular stimulus modalities. Alternatively, GRIA1 may play a role in selective learning when the similarity between cues competing for learning is high, as for flavour preference learning, but not when low, as for auditory and visual cues.