Social modulation of associative fear learning by pheromone communication

Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned familiar mouse and by the putative stress-related anxiogenic pheromone β-phenylethylamine (β-PEA). Together, these findings suggest social modulation of higher-order cognitive processing through pheromone communication and support the concurrent excitor hypothesis of extinction learning.Social communication in mammals has evolved to facilitate reproductive behavior and for protection against environmental threat and predation. Mice communicate information about imminent danger through vocal (Seyfarth and Cheney 2003), visual (Kavaliers et al. 2001; Langford et al. 2006), and odor or pheromone cues (Rottman and Snowdon 1972), each with profound influences on defensive responding. There is also evidence of social empathy in mice (Langford et al. 2006). Mice will sensitize to pain-inducing stimuli simply by observing a conspecific that is currently experiencing pain. Importantly, sensitization occurs only when the conspecific is familiar with the observer (i.e., sibling or cage mate), a clear example of social modulation of an innate behavior. Müller-Velten (1966) provided the first evidence of a functional alarm chemosignal in mice by showing that animals would avoid a pathway in which the odor of a stressed mouse was present. Subsequent studies have shown effects of mammalian olfactory chemosignals on a variety of defensive behaviors such as analgesia, vigilance, and avoidance (Rottman and Snowdon 1972; Mackay-Sim and Laing 1981; Fanselow 1985; Zalaquett and Thiessen 1991). To date, research on social modulation of behavior has focused primarily on observational learning and innate or nonassociative processes. Two recent studies have demonstrated an influence of fear-related chemosignals on associative learning in humans (Chen et al. 2006; Prehn et al. 2006), evidence that supports the hypothesis that social modulation of behavior extends to higher-order cognitive processing.In the following experiments, we asked whether exposure to a familiar mouse recently fear conditioned or trained for fear extinction would influence associative fear learning in a conspecific. We find that exposure to a recently fear-conditioned mouse impairs acquisition of conditioned fear, while the same experience facilitates the extinction of conditioned fear; effects mimicked by exposure to an olfactory chemosignal emitted from fear-conditioned mice and by the putative anxiogenic pheromone, β-phenylethylamine (β-PEA). Interestingly, we find that exposure to a recently extinction-trained mouse results in an inhibition of fear extinction learning, an effect not related to an olfactory chemosignal emitted by a recently extinguished mouse or by exposure to β-PEA. These data suggest that mice communicate information about their experience, in part through pheromone communication, with different effects on associative learning depending on the valence of the task.