An alternative inhibitory avoidance task for studying hippocampus-dependent spatial aversive memory in mice

In natural environments, animals must navigate to goals while avoiding　potential danger, making adaptive route choice crucial for survival. However, behavioral tasks for quantitatively evaluating avoidance through route choice during spatial navigation remain limited in mice, and the neural mechanisms underlying experience-dependent updating of route choice remain incompletely understood. Here, we established an air puff-based alternative inhibitory avoidance (AIA) task in mice to examine how aversive experience modifies a previously learned route preference. Water-restricted mice were first trained for 3 consecutive days to prefer a short path for obtaining water reward. They were then trained to avoid this preferred short path by receiving an air puff at its center when they passed through it. Mice that received only 3 air puffs showed lower avoidance behavior at the 6-h memory test. In contrast, mice that continued to receive air puffs until they rarely selected the short path during training showed significantly stronger avoidance at the 6-h test, and this avoidance was also observed at the 24-h test. We next examined whether hippocampal activity is required for retrieval of aversive memory in the AIA task. Chemogenetic suppression of hippocampal activity 30 min before the 6-h test impaired retrieval of aversive memory. Together, these results indicate that the AIA task provides a useful behavioral paradigm for assessing experience-dependent changes in route choice based on aversive events in mice, and that retrieval of this spatial aversive memory depends on hippocampal activity.