The long-term stability of new hippocampal place fields requires new protein synthesis

Abstract

The hippocampus is critical for formation of spatial memories. Hippocampal pyramidal neurons in freely behaving animals exhibit spatially selective firing patterns, which taken together form an internal representation of the environment. This representation is thought to contribute to the hippocampal spatial memory system. Behavioral long-term memories differ from short-term memories in requiring the synthesis of new proteins. Does the development of the internal hippocampal representation also require the synthesis of new proteins? We found that blocking protein synthesis in the brain of mice by 95% does not affect short-term stability of newly formed hippocampal place fields but abolishes stability in the long term. By contrast, inhibiting protein synthesis does not affect the retention and recall of previously established fields in a familiar environment, indicating that protein synthesis-dependent reconsolidation is not required for recall. Our results indicate that place fields parallel both behavioral memories and the late phase of long-term potentiation in requiring the synthesis of new proteins for consolidation.

Fig. 1.

Experimental protocol. Recordings were made on 2 consecutive days. On the first day, at least two cells were identified and recorded in the familiar environment, shown here as a white cylinder with a black cue. This was followed by a session in a novel environment: a cylinder of the same size but of a different color, and with different cues on its walls. Immediately after removal from the novel environment, the animal was injected with either drug or saline. The gray box indicates the duration of protein synthesis inhibition. We recorded from the animals in both the novel and familiar environments at 1, 6, and 24 h postinjection.

Fig. 2.

Firing fields in familiar and novel environments. Examples of the firing fields of four cells from a saline-injected mouse and four cells from an anisomycin-injected mouse. (A and B) Place fields of saline-injected mouse in familiar (A) and novel (B) environments. Firing-rate maps for each pyramidal cell are shown as a row. The rate maps are shown in the time order they were performed. (C and D) Place fields of anisomycin-injected mouse in familiar (C) and novel (D) environments. Each square pixel in a rate map represents a 2 × 2-cm area in the apparatus. Yellow encodes regions where the animal visited and the cell never fired. Orange, red, green, blue, and purple pixels encode progressively higher firing rates and are autoscaled in each session. (Peak firing rates for all cells are in Table 1.) White pixels were not visited. (E) Waveforms of the four cells from the saline-injected mouse shown in A and B, during the first and last session of the experiment. (F) Waveforms of the four cells from the anisomycin-injected mouse shown in C and D, during the first and last session of the experiment.

Fig. 3.

Similarity scores for the familiar and novel environments. Comparisons of firing pattern similarity in pairs of sessions at the 1-, 6-, and 24-h time points, in the novel (A) and familiar (B) environments. Firing patterns at each time point were compared with the previous session in that environment. Each comparison is shown as two bars indicating the mean similarity score (±SEM) for saline-injected mice (gray, n = 28 cells at the 6-h time point from five animals) and anisomycin-injected mice (black, n = 34 cells at the 6-h time point from six animals). Asterisk indicates statistical significance by a two-tailed Student's t test (P = 0.0009).

Fig. 4.

Coherence and information content values in the familiar and novel environments. Coherence (A) and information content (B) of place cell rate maps in the familiar and novel environments. Each bar represents the pooled data from all sessions recorded in that environment. The two bars indicate the mean similarity score (±SEM) for saline-injected (gray) and anisomycin-injected (black) mice.