Abstract
BackgroundDeciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. During the past decade, the three-chamber test has become such a standard paradigm used to evaluate social preference (sociability) and social novelty preference in mice. This test suffers from several caveats, including its reliance on spatial navigation skills and negligence of behavioral dynamics.MethodsHere, we present a novel experimental apparatus and an automated analysis system which offer an alternative to the three-chamber test while solving the aforementioned caveats. The custom-made apparatus is simple for production, and the analysis system is publically available as an open-source software, enabling its free use. We used this system to compare the dynamics of social behavior during the social preference and social novelty preference tests between male and female C57BL/6J mice.ResultsWe found that in both tests, male mice keep their preference towards one of the stimuli for longer periods than females. We then employed our system to define several new parameters of social behavioral dynamics in mice and revealed that social preference behavior is segregated in time into two distinct phases. An early exploration phase, characterized by high rate of transitions between stimuli and short bouts of stimulus investigation, is followed by an interaction phase with low transition rate and prolonged interactions, mainly with the preferred stimulus. Finally, we compared the dynamics of social behavior between C57BL/6J and BTBR male mice, the latter of which are considered as asocial strain serving as a model for autism spectrum disorder. We found that BTBR mice (n = 8) showed a specific deficit in transition from the exploration phase to the interaction phase in the social preference test, suggesting a reduced tendency towards social interaction.ConclusionsWe successfully employed our new experimental system to unravel previously unidentified sex- and strain-specific differences in the dynamics of social behavior in mice. Thus, the system presented here facilitates a more thorough and detailed analysis of social behavior in small rodent models, enabling a better comparison between strains and treatments.
Highlights
Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner
We demonstrate the ability of this system to measure novel parameters of murine social behavior, to detect previously unidentified sex- and strain-specific differences in the dynamics of social preference and social novelty preference
Using the ability of this system to measure new parameters of social investigation, we demonstrated sex- and strain-specific differences in the dynamics of social behavior during the SNP (Fig. 5g) tests (SP) and SNP tasks
Summary
Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. Unraveling the biological mechanisms underlying pathological conditions characterized by atypical social behavior, such as autism spectrum disorder (ASD), is currently one of the main challenges in the field of social neuroscience [1] Addressing this challenge requires the use of standard behavioral paradigms that typify the behavior of animal models in an unbiased way. The test, based on measuring the time spent by the subject in either a central chamber or each of two lateral chambers where distinct stimuli are located, suffers from several caveats It largely depends on the preference of the subject to locate itself in one of the chambers, should be sensitive to parameters that influence spatial navigation, memory, and preference. This test is mostly used to measure the total time spent by the subject in each of the chambers, while neglecting the behavioral dynamics
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