Putting fear in its place: remapping of hippocampal place cells during fear conditioning

Abstract

We recorded hippocampal place cells in two spatial environments: a training environment in which rats underwent fear conditioning and a neutral control environment. Fear conditioning caused many place cells to alter (or remap) their preferred firing locations in the training environment, whereas most cells remained stable in the control environment. This finding indicates that aversive reinforcement can induce place cell remapping even when the environment itself remains unchanged. Furthermore, contextual fear conditioning caused significantly more remapping of place cells than auditory fear conditioning, suggesting that place cell remapping was related to the rat's learned fear of the environment. These results suggest that one possible function of place cell remapping may be to generate new spatial representations of a single environment, which could help the animal to discriminate among different motivational contexts within that environment.

Figure 1.

Experimental design. a, Rats foraged for food pellets in two different chambers (training and control boxes) (see Materials and Methods). b, The CS consisted of a sequence of white-noise pips, and the US, a sequence of electric shocks delivered to the eyelid. c, Rats were preexposed (pre-exp.) for 15 min to each box on the day before conditioning. Three sessions—habituation, acquisition, and test—were given in the training box over a total time period of ∼4 hr. Place cell activity was recorded during place map sessions conducted in the training (open) and control (shaded) boxes at time points indicated in the diagram.

Figure 4.

Example place maps. a, Four place maps [showing preconditioning (pre-cond.) and postconditioning (post-cond.) maps in the control box and training box] are plotted for each of four cells (one from the cued and three from the context group). Color-coded firing rates at each location in the box are plotted as a percentage of a scaling factor, equal to 2 SDs above the mean firing rate (in Hertz) of the cell, shown at top right of each map (white space indicates undersampled pixels) (see Materials and Methods). Pixel-by-pixel correlations (r) between preconditioning and postconditioning maps are shown below each pair of maps. Representative spike traces for each cell in each session are depicted at the top left of each map, and calibration, showing 200 μV (vertical) and 1 msec (horizontal), is plotted in the bottom left corner for each cell.

Figure 5.

Partial remapping of hippocampal place cells. Examples of two place cells (one stable and one remapping) recorded simultaneously from the same rat from the context group. Traces, mean firing rates, and correlation indices between maps are shown as in Figure 4. pre-cond., Preconditioning; post-cond., postconditioning.

Figure 6.

Within-session stability of place fields (example cell). On the top row, two maps show the place-specific activity of this cell during the entire place map session before (left) and after (right) conditioning in the training box. On the bottom row, each place map session is divided into two halves (∼5 min/half). Note that, within each session (both before and after conditioning), the place field remained stable, despite the fact that this cell remaps its firing field after conditioning. Mean firing rates and correlation indices are shown as in Figure 4, and traces are shown next to the preconditioning (pre-cond.) and postconditioning (post-cond.) place maps.

Figure 2.

Behavioral analysis of fear conditioning. a, Bar graph shows mean and SE of conditioning-induced increase in freezing behavior, averaged over all rats in the cued (n = 8) and context (n = 8) groups. Training box data compare the 10 min period immediately after the last acquisition trial with the 10 min place map period immediately preceding the first acquisition trial; control box data compare the preconditioning versus postconditioning place map sessions. b, Mean postconditioning freezing behavior to the auditory CS (measured during the test session) and training context (measured during the first 10 min of the postconditioning place map session in the training box) for all rats in the cued (n = 8) and context (n = 8) groups. ^*p ≤ 0.05; ^*** p ≤ 0.001.

Figure 3.

Electrode placement. Coronal section of dorsal hippocampus. The arrowhead indicates the lesion left by passing current through the tip of the recording electrode at the end of the experiment.

Figure 7.

Difference in remapping between the cued and context groups. a, Bars show the mean and SE of the correlation index of the preconditioning versus postconditioning place maps in the training (r_T) and the control (r_C) box for cells from the context group and cued group. b, Rank-ordered distributions of the normalized r_T scores for cells from the context (n = 22) and cued (n = 24) groups that had a place field in the training box. Negative scores indicate more remapping of the training than the control box, whereas positive scores indicate more remapping of the control than the training box.

Figure 8.

θ Rhythm. Each panel shows the power spectrum (bin width, 0.0256 Hz) of the hippocampal multiunit recording signal during place map sessions in the training box. Shaded region indicates the θ band (6-8 Hz).