Social recognition in laboratory mice requires integration of behaviorally-induced somatosensory, auditory and olfactory cues.

In humans, discrimination between individuals, also termed social recognition, can rely on a single sensory modality, such as vision. By analogy, social recognition in rodents is thought to be based upon olfaction. Here, we hypothesized that social recognition in rodents relies upon integration of olfactory, auditory and somatosensory cues, hence requiring active behavior of social stimuli. Using distinct social recognition tests, we demonstrated that adult male mice do not exhibit recognition of familiar stimuli or learn the identity of novel stimuli that are inactive due to anesthesia. We further revealed that impairing the olfactory, somatosensory or auditory systems prevents behavioral recognition of familiar stimuli. Finally, we found that familiar and novel stimuli generate distinct movement patterns during social discrimination and that subjects react differentially to the movement of these stimuli. Thus, unlike what occurs in humans, social recognition in mice relies on integration of information from several sensory modalities.

Impaired sex preference, but not social and social novelty preferences, following systemic blockade of oxytocin receptors in adult male mice.

The hypothalamic neuropeptide oxytocin (OT) is a powerful modulator of mammalian social behavior and its administration was shown to affect various types of social interactions. However, systematic examinations of the role of endogenous OT release in social behavior have heretofore been done only using genetically modified animal models in which the genes encoding either OT or the OT receptor (OTR) were mutated. While such genetic manipulations revealed various behavioral deficits, these deficits may involve developmental or long-term processes and do not prove the participation of acute OT release in the impaired behavior. Here we used a battery of social discrimination tasks to evaluate the effects of acute systemic OTR blockade, using a non-peptide, orally active OTR antagonist (L368,899), on social behavior of adult male C57BL/6 J mice. We found no effect of the pharmacological manipulation on the social preference and social novelty preference behaviors. However, the preference of a male mouse for investigating a female conspecific more than a male (sex preference behavior), was lost by administration of the OTR antagonist. Finally, we found that blocking OTR activity before social defeat prevented the consequent loss of social preference, suggesting a role for OT in the acquisition of aversive social memory. Overall, our results suggest that OT plays a role in modulating the salience of social stimuli and facilitating their memory, as predicted by the social salience theory, rather than in regulating the internal motivation of the subject for social interactions.

Distinct dynamics of social motivation drive differential social behavior in laboratory rat and mouse strains.

Mice and rats are widely used to explore mechanisms of mammalian social behavior in health and disease, raising the question whether they actually differ in their social behavior. Here we address this question by directly comparing social investigation behavior between two mouse and rat strains used most frequently for behavioral studies and as models of neuropathological conditions: C57BL/6 J mice and Sprague Dawley (SD) rats. Employing novel experimental systems for behavioral analysis of both subjects and stimuli during the social preference test, we reveal marked differences in behavioral dynamics between the strains, suggesting stronger and faster induction of social motivation in SD rats. These different behavioral patterns, which correlate with distinctive c-Fos expression in social motivation-related brain areas, are modified by competition with non-social rewarding stimuli, in a strain-specific manner. Thus, these two strains differ in their social behavior, which should be taken into consideration when selecting an appropriate model organism.

A System for Tracking the Dynamics of Social Preference Behavior in Small Rodents.

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and observer-independent manner. Since the beginning of the millennium, the three-chamber test has been widely used as a standard paradigm to evaluate sociability (social preference) and social novelty preference in small rodents. However, this test suffers from multiple limitations, including its dependence on spatial navigation and negligence of behavioral dynamics. Presented and validated here is a novel experimental system that offers an alternative to the three-chamber test, while also solving some of its caveats. The system requires a simple and affordable experimental apparatus and publicly available open-source analysis system, which automatically measures and analyzes multiple behavioral parameters at individual and population levels. It allows detailed analysis of the behavioral dynamics of small rodents during any social discrimination test. We demonstrate the efficiency of the system in analyzing the dynamics of social behavior during the social preference and social novelty preference tests as performed by adult male mice and rats. Moreover, we validate the ability of the system to reveal modified dynamics of social behavior in rodents following manipulations such as whisker trimming. Thus, the system allows for rigorous investigation of social behavior and dynamics in small rodent models and supports more accurate comparisons between strains, conditions, and treatments.

A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics.

BACKGROUND: 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. 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. METHODS: Here, 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. RESULTS: We 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. CONCLUSIONS: We 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.