Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage

Toshihiro Endo, Fumihiko Maekawa, Vootele Võikar, Asahi Haijima, Yukari Uemura, Yan Zhang, Wataru Miyazaki, Shigetomo Suyama, Kuniko Shimazaki, David P. Wolfer, Toshihiko Yada, Chiharu Tohyama, Hans Peter Lipp, Masaki Kakeyama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)


There has been a long-standing need to develop efficient and standardized behavioral test methods for evaluating higher-order brain functions in mice. Here, we developed and validated a behavioral flexibility test in mice using IntelliCage, a fully automated behavioral analysis system for mice in a group-housed environment. We first developed a " behavioral sequencing task" in the IntelliCage that enables us to assess the learning ability of place discrimination and behavioral sequence for reward acquisition. In the serial reversal learning using the task, the discriminated spatial patterns of the rewarded and never-rewarded places were serially reversed, and thus, mice were accordingly expected to realign the previously acquired behavioral sequence. In general, the tested mice showed rapid acquisition of the behavioral sequencing task and behavioral flexibility in the subsequent serial reversal stages both in intra- and inter-session analyses. It was found that essentially the same results were obtained among three different laboratories, which confirm the high stability of the present test protocol in different strains of mice (C57BL/6, DBA/2, and ICR). In particular, the most trained cohort of C57BL/6 mice achieved a markedly rapid adaptation to the reversal task in the final phase of the long-term serial reversal test, which possibly indicated that the mice adapted to the " reversal rule" itself. In conclusion, the newly developed behavioral test was shown to be a valid assay of behavioral flexibility in mice, and is expected to be utilized in tests of mouse models of cognitive deficits.

Original languageEnglish
Pages (from-to)172-181
Number of pages10
JournalBehavioural Brain Research
Issue number1
Publication statusPublished - 2011 Aug 1
Externally publishedYes


  • Automated analysis
  • Behavioral flexibility
  • IntelliCage
  • Mouse
  • Serial reversal learning

ASJC Scopus subject areas

  • Behavioral Neuroscience


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