The effects of GluA1 deletion on the hippocampal population code for position.

The GluA1 subunit of AMPA receptors (AMPARs) is critical for hippocampal synaptic transmission and plasticity. Here, we measured the activity of single units from the CA1 region of the hippocampus while GluA1 knock-out (GluA1⁻/⁻) and wild-type (WT) mice traversed a linear track. Although overall firing rates were similar, GluA1⁻/⁻ neurons were more likely to spike in bursts, but at lower burst frequencies, compared with WT neurons. GluA1⁻/⁻ neurons showed large reductions in all measures of spatial and directional selectivity compared with WT neurons. Consistent with these alterations of single-neuron properties, the accuracy of the population code for position was substantially reduced in GluA1⁻/⁻, yet it is predicted to approach the accuracy of WT with increasing population size. The absolute representation of space, independent of movement direction, was greatly diminished in GluA1⁻/⁻ mice and is predicted to remain reduced even for larger populations. Finally, we found that the rate maps of GluA1⁻/⁻ neurons showed increased trial-by-trial variability but reduced experiential plasticity compared with the WT. These results reveal the critical contribution of GluA1-containing AMPARs to individual place cells and the hippocampal population code for space, which could explain the selective behavioral impairments observed in these mice.