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 us ed to study the cellular mechanisms underlying learning and memory mechanis ms in the hippocampus. A key assumption of many of these studies is that le sions of the hippocampus have a similar impact on learning and memory in mi ce and in rats. Here, we used axon-sparing ibotenate lesions to determine w hether damage to the hippocampus disrupts spatial learning and contextual c onditioning 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 keep ing the start site constant, nor prior training with the visible-platform t ask fully rescued the spatial learning deficits of the lesioned mice. As pr eviously 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 processi ng or motivation probably did not account for their deficits in the hidden- platform task. In contrast, the very same lesions did not affect either cue d or contextual fear conditioning. These results confirm the involvement of the hippocampus in spatial learning in mice, and they also demonstrate tha t hippocampal-lesioned mice can show contextual fear conditioning. Thus, th e behavioral findings presented here are crucial for the interpretation of transgenic experiments with the widely used water maze and fear-conditionin g paradigms. (C) 1999 Elsevier Science B.V. All rights reserved.