Contextual fear memories formed in the absence of the dorsal hippocampus decay across time

Abstract

Mammals suffering damage to the hippocampus display a dramatic loss of explicit, recently formed memories (retrograde amnesia). In contrast, deficits in the ability to form new memories following hippocampal damage (anterograde amnesia) can be overcome with sufficient training. By combining contextual fear conditioning with lesions of the dorsal hippocampus in rats, we discovered that while animals can form long-term contextual fear memories in the absence of the hippocampus, these memories decay with time, lacking the permanence that is a hallmark characteristic of normal fear memories. These findings indicate that while it is initially possible to acquire explicit memories when the hippocampus is compromised, these memories cannot transfer from a recent to remote state. This suggests that memories formed outside the hippocampus may nevertheless require the hippocampus to undergo systems consolidation, which has important clinical implications for the treatment of memory disorders.

Figure 1.

Representative photomicrographs show cresyl violet-stained coronal brain sections following excitotoxic lesions of the dorsal hippocampus (right) compared with sham controls (left). From top to bottom, the sections are 1.60, 2.60, 3.60, and 4.60 mm posterior to bregma.

Figure 2.

Longevity of a contextual fear memory formed in the absence of the hippocampus. A, Experimental design. B, Contextual fear acquisition. Mean (±SEM) freezing to the context during the 30 s period preceding each footshock (trial) for rats with an intact (sham) or damaged dorsal hippocampus (DH). All animals acquired contextual fear, regardless of lesion condition. C, Context fear test. Mean (±SEM) freezing to the context averaged over the 8 min context exposure test are displayed. Rats were tested 1, 3, 10, or 30 d following acquisition (retention interval). The 1 d test represents our measure of “recent” long-term memory, the 30 d test represents our measure of “remote” long-term memory. Sham rats maintained similar levels of freezing independent of retention interval. Animals conditioned in the absence of the DH exhibited compensatory contextual fear expression 1 d following training; however, the expression of this memory decayed dramatically across time. (n.s., not significant, p > 0.05; **p < 0.01; ***p < 0.001).