Medial prefrontal cortex supports recollection, but not familiarity, in the rat

Abstract

There is continuing controversy about the extent to which the rodent medial prefrontal cortical area (mPFC) is functionally homologous to the dorsolateral prefrontal cortex in humans and nonhuman primates. Previous studies have compared the effects of mPFC lesions in rats to those of dorsolateral prefrontal lesions in working memory, strategy switching, and temporal ordering. None, however, has examined the role of the rodent mPFC in recognition memory, wherein, in humans, dorsolateral prefrontal damage results in a deficit in source monitoring resulting in impaired recollection. In the present study, we examined recognition memory in rats with bilateral mPFC lesions (prelimbic/infralimbic regions; ibotenic acid) using a variant of a non-match-to-sample task with manipulations of response bias that allowed for a signal detection analysis that distinguishes recollection and familiarity contributions to recognition memory. Animals with medial prefrontal lesions had a modest overall deficit in recognition with no general change in their tendency to elicit "old" or "new" responses. Signal detection analyses indicated that rats with mPFC damage had a curvilinear and symmetrical receiver operating characteristic (ROC) curve, compared with a curvilinear and asymmetrical ROC curve in control subjects, indicating that mPFC damage severely reduced recollection-based performance, while sparing familiarity. The recollection failure was associated with an impaired ability to reject new items (increased false alarm rate), whereas the identification of old items (hit rate) was normal. This pattern of findings is similar to that observed in humans with dorsolateral prefrontal damage and is complementary to the selective deficit in hit rate observed after hippocampal damage.

Figure 1.

Recognition memory task. During the sample phase, animals were presented with 10 different odors, each baited with a Froot Loop reward. Then, after a 30 min delay, in the test phase, subjects were required to distinguish the 10 odors that were presented during the sample stage from 10 new odors that had not been presented previously on that day. If a test odor was new, the animal could dig in the cup to retrieve the reward. Conversely, if a test odor was old, the animal was required to withhold digging in the test stimulus cup and instead approach an empty cup in the back of the home cage to obtain reward. The order of old and new test odors was randomized. Response bias was manipulated by varying the height of the cup and the amount of reward (number of Froot Loops) received for responding or withholding responses to the target cup.

Figure 2.

Medial prefrontal lesions. Shown is a reconstruction of bilateral medial prefrontal lesions at 3.20, 2.20, and 1.20 mm anterior to bregma. Black, Lesion common to all rats; light gray, average lesion across animals; dotted line, largest lesion.

Figure 3.

ROC function in recognition performance for control subjects and rats with medial prefrontal damage. A, ROC for control and mPFC animals before surgery. B, Postoperatively, control animals continued to exhibit an asymmetrical and curvilinear ROC, whereas the ROC function of rats with mPFC damage was curvilinear but symmetrical. Note that the rightward shifts in the scores at each bias level reflect increases in the false alarm rate at each bias. No change in the hit rate (which would be observed as the vertical displacement between corresponding scores) was evident at any bias level. C, Parameter estimates of recollection (R) and familiarity (d′) for controls and lesioned animals after surgery (*p < 0.05). Error bars show SEM.

Figure 4.

Hit and false alarm rates for control subjects and rats with medial prefrontal damage. The hit rates (A) and false alarm rates (B) are shown for each response bias level (1–5). The increase in false alarm rate was particularly large at the more conservative bias levels (bias 5, **p < 0.001; bias 4, *p < 0.05). There was no effect of the lesion on the hit rate at any bias level. Error bars show SEM.