Major mental illnesses such as schizophrenia and the Autism Spectrum Disorder, which affect millions of people, share a common symptom, the afflicted people do not respond adaptively to social cues. This unifying feature has helped call attention to the importance of understanding the behavioral, genomic, neural, and developmental foundations of sociality, for these are the substrates on which these devastating diseases are manifested. Modern biomedical approaches to recognizing, analyzing, and remediating such disorders require animal models, and this SBIR Phase I proposal presents a novel approach to behavioral phenotyping that reveals the onset and development of sociality in mice, and can recognize deviations from normal development. Traditionally, behavioral phenotyping uses categorical measures, such as exploration, sleep, anxiety, feeding, aggression, etc. Our approach departs from this tradition and instead uses kinematic measures of individuals in a group context. We monitor continuous parameters such as activity/inactivity, position, contact, group size and configuration. We have the laboratory foundation for studying group behavior and individuals'behavior in the group;it is now possible to move the approach from the lab to the marketplace. Star Enterprises has an excellent history in designing and building automated, well-controlled habitats for rodents (used in spaceflight research) and can combine that expertise with its knowledge of behavioral development in mice and rats. We will create a controlled testing environment in which groups of infant mice are observed by video camera at 8-, 12-, and 16- days of age. Plug-in programs will automatically analyze 20-min digitized video samples to detect the onset of sociality, recognizing the developmental appearance of coupled activity among the individuals in the group, and by patterns of aggregon formation shown by the group as unit. Groups will also be analyzed at the level of the individual. These group and individual data will be correlated to behavioral data of the same mice as independent, pre-pubertal juveniles and as adults, using more traditional phenotyping measures. Thus, we can both develop our new methods and cross-validate them with conventional indices. Finally, we will further demonstrate the sensitivity, power, and practical application of these methods by using them with mutant mice containing genetically-engineered knock-out deficits known to affect sociality.
Accurately assessing the development of behavior and sociality is critical in developing and using animal models for human behavioral and mental disorders. The behavioral protocols and tools we develop will facilitate the creation of behavioral-disorder animal models and make possible accurate and reliable measures of sociality throughout development, which will serve the mental health research community, including the laboratory, pharmaceutical, and biotechnology sectors.
Using a novel approach to behavioral measurement, we will create an apparatus (hardware and software) that will enable scientists to rapidly assess whether laboratory mice are developing normal social behavior. Such biomedical assessment tools are urgently needed for studying and remediating illnesses such as autism and schizophrenia that involve alterations in responses to social cues.
|Koyama, Sachiko; Soini, Helena A; Wager-Miller, James et al. (2015) Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5- dihydrothiazole in female mice. Proc Biol Sci 282:|