There is wide agreement that spatial memory is dependent on the integrity of the hippocampus, but the importance of the hippocampus for nonspatial tasks, including tasks of object recognition memory is not as clear. We examined the relationship between hippocampal lesion size and both spatial memory and object recognition memory in rats. Spatial memory was impaired after bilateral dorsal hippocampal lesions that encompassed 30 -50% total volume, and as lesion size increased from 50% to Ϸ100% of total hippocampal volume, performance was similarly impaired. In contrast, object recognition was intact after dorsal hippocampal lesions that damaged 50 -75% of total hippocampal volume and was impaired only after larger lesions that encompassed 75-100% of hippocampal volume. Last, ventral hippocampal lesions that encompassed Ϸ50% of total hippocampal volume impaired spatial memory but did not affect object recognition memory. These findings show that the hippocampus is important for both spatial memory and recognition memory. However, spatial memory performance requires more hippocampal tissue than does recognition memory.
New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior.
In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.
Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks. It has also figured prominently in theoretical treatments of memory and hippocampal function. Yet temporally graded retrograde amnesia has not been demonstrated following hippocampal damage in spatial tasks like the water maze. We have assessed recent and remote spatial memory following hippocampal lesions in three different tests of spatial memory: (1) the standard water maze; (2) the Oasis maze, a dry-land version of the water maze; and (3) the annular water maze, where training and testing occur within a circular corridor. Training protocols were developed for each task such that retention of spatial memory could be expressed after very long retention intervals. In addition, retention in each task was assessed with single probe trials so that the assessment of remote memory did not depend on the ability to relearn across multiple trials. The findings were consistent across the three tasks. In the standard water maze (Experiment 1), spatial memory was impaired after training-surgery intervals of 1 day, 8 weeks, or 14 weeks. Similarly, in the Oasis maze (Experiment 2), spatial memory was impaired after trainingsurgery intervals of 1 day and 9 weeks. Finally, in the annular water maze (Experiment 3), spatial memory was impaired after training-surgery intervals of 9 weeks and 14 weeks. Dorsal hippocampal lesions impaired performance to the same extent as complete lesions. The impairment in remote spatial memory could reflect disruption of previously acquired spatial information. Alternatively, it is possible that in these tasks hippocampal lesions might produce an impairment in performance that prevents the expression of an otherwise intact spatial memory.
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