Automated behavioral analysis of mice using INTELLICAGE:
Inter-laboratory comparisons and validation with exploratory behavior
and spatial learning
H.-P. Lipp1, O. Litvin2, M. Galsworthy1,
D.L. Vyssotski2, A.L. Vyssotski1, A.E. Rau1,
F. Neuhäusser- Wespy1, H. Würbel3, R.
Nitsch2 and D.P. Wolfer1
1Institute of Anatomy and 2Dept.
of Psychiatry Research, University of Zürich, Zürich, Switzerland
3Institute of Veterinary Physiology, University of Giessen, Giessen,
Germany
INTELLICAGE is a large home cage containing four complete operant
conditioning units
placed in the corners. A central computer continuously controls and monitors
activity and
learning of up to 16 transponder-tagged mice per cage without human interference.
In a recent standardized multi-lab study, we noted identical strain rank
order in the open-field, elevated Null-maze, water maze and object exploration,
but comparison of absolute values revealed significant differences between
laboratories, or strain-by-laboratory interactions. A subset of 46 female
mice was also tested in 4 INTELLICAGES, located in different animal facilities
of the University of Zurich (2 cages per site), each unit housing 11-
12 transponder-tagged mice from different strains. The system measured
continually visits of drinking sides, development of place preference
and activity parameters. INTELLICAGE revealed significant strain differences
in initial exploratory activity and baseline activity during the first
day. Most importantly, the behavioral scores of the strains as observed
in both laboratories were statistically indistinguishable.
We then compared the first 10 min after introduction to INTELLICAGE with
standard tests of exploration lasting about the same time span. The measure
in INTELLICAGE was the number of visits to the yet unfamiliar test corners.
It was positively correlated with visits to the center in the open-field.
For the elevated Null-maze, the number of head dips correlated strongly
with the number of corner visits in INTELLICAGE, while measures of anxiety
such as time in the protected area did not correlate significantly. In
the water maze (WM), we found a significant positive correlation between
average escape latencies and place preference learning in INTELLICAGE.
No correlations were found with WM probe trial scores. These findings
indicate that either test measures the acquisition of spatial learning,
but the WM testing took four man-weeks, while INTELLICAGE showed the same
findings after 24 hours without presence of an experimenter.
We conclude that optimal standardization and comparability is best achieved
by the use of
automated procedures, and that such automation measures the same behavioral
dimensions
as standard manual tests, yet with much less stress for animals and experimenters.
Supported by SNF, the NCCR Neural Plasticity and Repair
and the Foundation 3R.
Paper presented
at Measuring Behavior 2005
, 5th International Conference on Methods and Techniques
in Behavioral Research, 30 August - 2 September 2005, Wageningen, The
Netherlands.
© 2005 Noldus
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