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

Overview

1. Research Center for Idling Brain Science, University of Toyama,Toyama, 930-0194 Japan
2. Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama,Toyama, 930−0194 Japan
3. CREST, Japan Science and Technology Agency (JST), University of Toyama,Toyama, Japan
4. Japan Agency for Medical Research and Development (AMED),Tokyo, Japan

Abstract

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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13041-026-01308-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• figshare:32737954, at figshare; found in DataCite
• figshare:32737957, at figshare; found in DataCite
• figshare:32737960, at figshare; found in DataCite

Data availability

No datasets were generated or analysed during the current study.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 5 keywords, 8 MeSH terms, 10 funders, 15 references.

Cite

This paper

Wang, H., Nomoto, M., Murayama, E., Yamada-Nomoto, K., & Inokuchi, K. (2026). An alternative inhibitory avoidance task for studying hippocampus-dependent spatial aversive memory in mice. Molecular brain, 19(1), 47. https://doi.org/10.1186/s13041-026-01308-z

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