Automated Measurement of Mouse Freezing Behavior and its Use for Quantitative Trait Locus Analysis of Contextual Fear Conditioning in (BALB/cJ × C57BL/6J)F2 Mice
- Verónica S. Valentinuzzi1,2,
- Daniel E. Kolker1,
- Martha Hotz Vitaterna1,
- Kazuhiro Shimomura1,4,
- Andrew Whiteley1,4,
- Sharon Low-Zeddies1,
- Fred W. Turek1,
- Elenice A.M. Ferrari2,
- Richard Paylor3,6, and
- Joseph S. Takahashi1,4,5
- 1Center for Circadian Biology and Medicine, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208 USA, 2Laboratório de Sistemas Neurais e Comportamento, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, 13083-970, Brazil, 3Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, Maryland 20892 USA, 4Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208 USA
Abstract
The most commonly measured mouse behavior in fear conditioning tests is freezing. A technical limitation, particularly for genetic studies, is the method of direct observation used for quantifying this response, with the potential for bias or inconsistencies. We report the use of a computerized method based on latency between photobeam interruption measures as a reliable scoring criterion in mice. The different computer measures obtained during contextual fear conditioning tests showed high correlations with hand-scored freezing; r values ranged from 0.87 to 0.94. Previously reported strain differences between C57BL/6J and DBA/2J in context-dependent fear conditioning were also detected by the computer-based system. In addition, the use of computer-scored freezing of 199 (BALB/cJ × C57BL/6J)F2 mice enabled us to detect a suggestive gender-dependent chromosomal locus for contextual fear conditioning on distal chromosome 8 by QTL analysis. Automation of freeze scoring would significantly increase efficiency and reliability of this learning and memory test.
