Time-dependent relationship between the dorsal hippocampus and the prefrontal cortex in spatial memory

Abstract

The prefrontal cortex and the dorsal hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.

Fig. 1.

Illustration of the positions of the cannulas and the extent of damage by excitotoxic lesions in a series of sections of mPFC and dorsal hippocampus. a, Histological verification of the HP/LES (or HP/CT)+mPFC/drug group. Cannula positions are marked in mPFC (○, HP/CT+mPFC/drug group; ●, HP/LES+mPFC/drug group). The largest and the smallest tissue damage produced by ibotenic acid in the dorsal hippocampus (i.e., HP/LES+mPFC/drug group) are shown by gray andblack, respectively. b, Histological verifications of the mPFC/LES (or mPFC/CT)+HP/drug group. Cannula positions are shown in the dorsal hippocampus (○, mPFC/CT+HP/drug group; ●, mPFC/LES+HP/drug group). The largest and the smallest tissue damage produced by quinolinic acid in mPFC are shown bygray and black, respectively. The anteroposterior stereotaxic coordinates for the sections were shown by the numbers beside the sections (in millimeters) (modified from Paxinos and Watson, 1997).

Fig. 2.

Postsurgery performance in a short-term spatial water maze task. a, Choice accuracy for two blocks with PBS injections into either the dorsal hippocampus or mPFC after surgery (1 block is 2 d of 8 trials per day). Note the initial deficit in both lesion groups (but more severely in the mPFC/LES group) in block 1 yet with improvement in block 2.b, Average activity levels of different lesion groups during postsurgery performance in the spatial working memory task (Study arm duration, the time spent on a study arm;Choice latency, the latency to reach the end of a choice arm from the center platform). There were no significant differences among the groups. CT, Control group;HP/LES, the group with dorsal hippocampal lesions and PBS injections into mPFC; mPFC/LES, the group with mPFC lesions and PBS injections into the dorsal hippocampus.

Fig. 3.

Choice accuracy in different lesion groups after the injection of PBS or MUS in 10 sec or 5 min delay trials.a, The hippocampal control lesion group (HP/CT) exhibited no difference in choice accuracy between the conditions with MUS and PBS injections into mPFC.b, The mPFC control lesion group (mPFC/CT) showed lower choice accuracy only in 5 min delay trials with MUS injection into the dorsal hippocampus compared with PBS injection. c, Compared with PBS injection, the hippocampal lesion group (HP/LES) showed a marked deficit in choice accuracy only in 10 sec delay trials with MUS injection into mPFC. Both PBS and MUS injections disrupted performance in 5 min delay trials in the hippocampal lesion group.d, The mPFC lesion group (mPFC/LES) was impaired in both delay conditions (i.e., 10 sec and 5 min) when MUS was injected into the dorsal hippocampus compared with PBS injection.

Fig. 4.

Average activity levels for different groups during 10 sec and 5 min delay trials (Study arm duration, the time spent on a study arm; Choice latency, the latency to reach the end of a choice arm from the center platform). No significant differences were found among the groups when MUS was injected.