Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice

J Neurosci Methods. 2014 Mar 15:224:48-57. doi: 10.1016/j.jneumeth.2013.12.010. Epub 2013 Dec 31.

Abstract

Background: Behavioral assessment of mutant mouse models and novel candidate drugs is a slow and labor intensive process. This limitation produces a significant impediment to CNS drug discovery.

New method: By combining video and vibration analysis we created an automated system that provides the most detailed description of mouse behavior available. Our system (The Behavioral Spectrometer) allowed for the rapid assessment of behavioral abnormalities in the BTBR model of Autism, the restraint model of stress and the irritant model of inflammatory pain.

Results: We found that each model produced a unique alteration of the spectrum of behavior emitted by the mice. BTBR mice engaged in more grooming and less rearing behaviors. Prior restraint stress produced dramatic increases in grooming activity at the expense of locomotor behavior. Pain produced profound decreases in emitted behavior that were reversible with analgesic treatment.

Comparison with existing method(s): We evaluated our system through a direct comparison on the same subjects with the current "gold standard" of human observation of video recordings. Using the same mice evaluated over the same range of behaviors, the Behavioral Spectrometer produced a quantitative categorization of behavior that was highly correlated with the scores produced by trained human observers (r=0.97).

Conclusions: Our results show that this new system is a highly valid and sensitive method to characterize behavioral effects in mice. As a fully automated and easily scalable instrument the Behavioral Spectrometer represents a high-throughput behavioral tool that reduces the time and labor involved in behavioral research.

Keywords: Automated detection; Behavioral screening; Ethological analysis; Grooming; Neurobehavioral assessment; Video analysis.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Autistic Disorder / physiopathology*
  • Autistic Disorder / psychology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Carrageenan / toxicity
  • Disease Models, Animal
  • Electronic Data Processing
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Naproxen / toxicity
  • Pain / diagnosis*
  • Pain / etiology
  • Reproducibility of Results
  • Restraint, Physical / methods
  • Stress, Psychological / diagnosis
  • Stress, Psychological / etiology
  • Stress, Psychological / physiopathology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Naproxen
  • Carrageenan