Experience-dependent increase in CA1 place cell spatial information, but not spatial reproducibility, is dependent on the autophosphorylation of the alpha-isoform of the calcium/calmodulin-dependent protein kinase II

Abstract

Place cells in hippocampal area CA1 are essential for spatial learning and memory. Here, we examine whether daily exposure to a previously unexplored environment can alter place cell properties. We demonstrate two previously unreported slowly developing plasticities in mouse place fields: both the spatial tuning and the trial-to-trial reproducibility of CA1 place fields improve over days. We asked whether these two components of improved spatial coding rely on the alpha-isoform of the calcium/calmodulin-dependent protein kinase II (alphaCaMKII) autophosphorylation, an effector mechanism of NMDA receptor-dependent long-term potentiation and an essential molecular process for spatial memory formation. We show that, in mice with deficient autophosphorylation of alphaCaMKII, the spatial tuning of place fields is initially similar to that of wild-type mice, but completely fails to show the experience-dependent increase over days. In contrast, place field reproducibility in the mutants, although impaired, does show the experience-dependent increase over days. Consequently, the progressive improvement in spatial coding in new hippocampal place cell maps depends on the existence of two molecularly dissociable, experience-dependent processes.

Figure 1.

Two types of plastic changes in CA1 place cells of a wild-type mouse. A, Place fields of three cells simultaneously recorded over 4 d in a wild-type mouse. Spatial information increases across days. Firing rates shown as false color maps in which each color represents 10% of the peak firing rate. Numbers in white on each false-color map are peak firing rate, and numbers in black below are the spatial information scores. Data were taken from the third trial of each day. B, Graph of spatial information over the 4 d for the three cells shown in A. C, Graph of the spatial reproducibility measure over 4 d. Data were taken from the correlation of the second versus the third trial of each day.

Figure 2.

A, Spatial information increases over days in wild-type cells but not in mutant cells. Note that values are similar on day 1. B, Between-trial spatial reproducibility increases over exposure days in both wt and αCaMKII^T286A mice, although absolute levels of reproducibility are impaired in αCaMKII^T286A mice. Error bars indicate SEM. C, D, Representative examples of wt (C) and αCaMKII^T286A (D) place cells recorded during two consecutive trials on days 1 and 4 (different cell populations on different days). Reproducibility values for trial 1 versus trial 2 comparison are shown in black boxes between the maps. Numbers in white on each false-color map are peak firing rates. Numbers at the bottom right of the trial 2 maps refer to the spatial information carried by the place cell (mean value for trial 1 and 2). Note how between-trial reproducibility is low in both mutants and wt on day 1 and higher on day 4. Spatial information content is higher on day 4 than on day 1 in the wt cells but fails to improve in the αCaMKII^T286A cells.

Figure 3.

A, B, Four simultaneously recorded cells from one wt (A) and one αCaMKII^T286A mouse (B) during a cue rotation experiment. Both sets of place fields rotate by a similar amount to the cue card during both the 180° rotation (trial B) and the return to baseline position (trial C).