Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination

Abstract

We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.

Fig. 1.

Experiment 1. Sample schematic view of within-subjects procedures. The animals were given remote conditioning in one context, and 50 d later they received recent training in a different context (with a different tone), followed by dorsal hippocampal or sham lesions 1 d later. After 10 d of recovery, they were given independent freezing tests for remote and recent, context and tone fear memory. The exact contexts and test orders used were counterbalanced. Drawings are not to scale.

Fig. 2.

Histological reconstruction of representative electrolytic lesion of the dorsal hippocampus.

Fig. 3.

Experiment 1. Temporally graded retrograde amnesia of contextual fear: within-subjects examination. A, Remote contextual fear. Rats that received DH lesions exhibited equivalent levels of freezing (% time ± SEM, for each minute of the 8 min test) as sham animals to the remotely acquired context, for which they were trained 50 d before the lesion.B, Recent contextual fear. The very same DH-lesioned rats exhibited a severe amnesia of contextual memory that was 1 d old at the time of the lesion. C, Context summary. This is the same data as in A and B, averaged for the first 6 min of each test (6 min was used to make the levels more comparable to the tone tests; see Fig. 4). DH-lesioned rats exhibited a severe but time-limited retrograde amnesia of contextual fear.

Fig. 4.

Experiment 1. Tone conditioning. For each test, the animal was placed into a novel context (C) and after a 2 min baseline (BL) period, a tone (remote or recent) played continuously for 6 min. A, Remote tone fear. DH-lesioned rats exhibited equivalent levels of freezing (% time ± SEM, for each minute of the 8 min test) as sham animals to the remotely acquired tone, for which they were trained 50 d before the lesion. B, Recent tone fear. DH-lesioned rats exhibited no deficit in freezing to the recently acquired tone, for which they were trained 1 d before the lesion. C, Tone summary. Same data as A and B, averaged for the 6 min that the tone was on. DH-lesioned rats exhibited normal levels of tone freezing.

Fig. 5.

Experiment 2. Further increase in the level of context fear relative to tone fear. Rats were trained only in one training context with one tone, and then given DH lesions 1 d later. A, Recent contextual fear. DH-lesioned animals exhibited a severe deficit in context freezing (% time ± SEM, for each minute of the 8 min test), although fear levels in sham animals were nearly asymptotic. B, Recent tone fear. DH-lesioned animals did not exhibit deficits in tone freezing, even as tone fear extinguished across the test period and became weaker.C, Interaction. Same data as A andB, averaged for the first 6 min of the context test and 6 min that the tone was on test (6 min was used to make the levels more comparable). DH-lesioned animals exhibited a deficit only in contextual freezing, although tone fear was substantially weaker than context fear in Sham animals.

Fig. 6.

Experiment 3. The generality of hippocampal hyperactivity. Rats were placed on a dark open field (lit only by a 25 W red bulb), and crossovers were scored for 4 min. Two bright lights (two 100 W white bulbs) were then shined onto the open field, and crossovers were scored for another 4 min. Open-field activity was assessed by scoring segment crossovers (mean ± SEM), which are depicted for each minute of the dark and light periods. DH-lesioned animals exhibited a robust hyperactivity during the dark phase of the test, but this hyperactivity disappeared when the lights were turned on. Moreover, hippocampal lesion-induced hyperactivity observed during the dark phase appeared to result from a lack of habituation that was seen in sham animals.