Ibotenate lesions of the hippocampus impair spatial learning but not contextual fear conditioning in mice.

Recently, gene targeting and other mouse transgenic techniques have been used to study the cellular mechanisms underlying learning and memory mechanisms in the hippocampus. A key assumption of many of these studies is that lesions of the hippocampus have a similar impact on learning and memory in mice and in rats. Here, we used axon-sparing ibotenate lesions to determine whether damage to the hippocampus disrupts spatial learning and contextual conditioning in mice, as it is known to do in rats. Our results demonstrated that hippocampal lesions impair performance in the hidden-platform version of the water maze under a variety of experimental conditions. Neither keeping the start site constant, nor prior training with the visible-platform task fully rescued the spatial learning deficits of the lesioned mice. As previously shown in rats, the lesions left the performance of the mice intact in the visible-platform version of the water maze, indicating that they do not affect all types of learning, and that disruptions of sensory processing or motivation probably did not account for their deficits in the hidden-platform task. In contrast, the very same lesions did not affect either cued or contextual fear conditioning. These results confirm the involvement of the hippocampus in spatial learning in mice, and they also demonstrate that hippocampal-lesioned mice can show contextual fear conditioning. Thus, the behavioral findings presented here are crucial for the interpretation of transgenic experiments with the widely used water maze and fear-conditioning paradigms.