Differential roles for hippocampal areas CA1 and CA3 in the contextual encoding and retrieval of extinguished fear

Abstract

Recent studies demonstrate that context-specific memory retrieval after extinction requires the hippocampus. However, the contribution of hippocampal subfields to the context-dependent expression of extinction is not known. In the present experiments, we examined the roles of areas CA1 and CA3 of the dorsal hippocampus in the context specificity of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock (unconditional stimulus or US), rats received extinction sessions in which the CS was presented without the US. In Experiment 1, pretraining neurotoxic lesions in either CA1 or CA3 eliminated the context dependence of extinguished fear. In Experiment 2, lesions of CA1 or CA3 were made after extinction training. In this case, only CA1 lesions impaired the context dependence of extinction. Collectively, these results reveal that both hippocampal areas CA1 and CA3 contribute to the acquisition of context-dependent extinction, but that only area CA1 is required for contextual memory retrieval.

Figure 1.

Representative photomicrographs showing four thionin-stained coronal sections along the septotemporal axis for CA1 and CA3 lesions in the dorsal hippocampus (Experiment 1).

Figure 2.

Schematic representation of brain lesions mapped onto coronal rat brain sections showing the minimum (black areas) and maximum (black> + gray areas) extent of CA1 or CA3 lesions (Experiment 1). Coordinates are given in millimeters from bregma.

Figure 3.

Effects of pre-training CA1 or CA3 lesions on fear conditioning, extinction, and testing (Experiment 1). (A) Percentage of freezing during the fear conditioning session for the three groups of rats. Freezing is shown for the 3-min period prior to the first trial (baseline) and during 1-min periods after each conditioning trial. (B) Percentage of freezing during the extinction sessions for the three groups of rats. Freezing was averaged across the 1-min periods after the first four CS presentations across the 3 d of extinction. (Inset) Freezing in three-trial blocks during the first extinction session. (C) Normalized conditional freezing across the retention test (CS freezing – baseline). Rats were tested either in the extinction context (SAME; open bars) or outside of the extinction context (DIFF; filled bars). Neurotoxic CA1, CA3, or sham (SH) lesions were made prior to conditioning. All data are presented as mean ± SEM.

Figure 4.

Effects of pre-training CA1 or CA3 lesions on context discrimination (Experiment 1). The figure shows the percentage of freezing for the first 10 min of context exposure during the first equilibration session. Exposure was either in the same context as the conditioning context (COND; open bars) or in a novel context (NOVEL; filled bars). Neurotoxic CA1, CA3, or sham (SH) lesions were made before conditioning. All data are presented as mean ± SEM.

Figure 5.

Representative photomicrographs showing four thionin-stained coronal sections along the septotemporal axis for each of subfield lesions in the dorsal hippocampus (Experiment 2).

Figure 6.

Schematic representation of brain lesions mapped onto coronal rat brain sections showing the minimum (black areas) and maximum (black + gray areas) extent of CA1 or CA3 lesions (Experiment 2). Coordinates are given in millimeters from bregma.

Figure 7.

Effects of post-extinction CA1 or CA3 lesions on fear conditioning, extinction, and testing (Experiment 2). (A) Percentage of freezing during the fear conditioning session for the three groups of rats. Freezing is shown for the 3-min period prior to the first trial (baseline) and during 1-min periods after each conditioning trial. (B) Percentage of freezing during the extinction sessions for the three groups of rats. Freezing was averaged across the 1-min periods after the first four CS presentations across the 3 d of extinction. Although lesion group designations are indicated in A and B, the rats had not undergone surgery at this point in training. (C) Normalized conditional freezing across the retention test (CS freezing − baseline). Rats were tested either in the extinction context (SAME; open bars) or outside of the extinction context (DIFF; filled bars). Neurotoxic CA1, CA3, or sham (SH) lesions were made after extinction. All data are presented as mean ± SEM.