Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli. However, whether this occurs in the context of natural communication, where stimulus significance is acquired through social interaction, has not been well investigated, perhaps because neural responses to species-specific vocalizations can be difficult to interpret within a systematic framework. The ultrasonic communication system between isolated mouse pups and adult females that either do or do not recognize the calls' significance provides an opportunity to explore this issue. We applied an information-based analysis to multi- and single unit data collected from anesthetized mothers and pup-naïve females to quantify how the communicative significance of pup calls affects their encoding in the auditory cortex. The timing and magnitude of information that cortical responses convey (at a 2-ms resolution) for pup call detection and discrimination was significantly improved in mothers compared to naïve females, most likely because of changes in call frequency encoding. This was not the case for a non-natural sound ensemble outside the mouse vocalization repertoire. The results demonstrate that a sensory cortical change in the timing code for communication sounds is correlated with the vocalizations' behavioral relevance, potentially enhancing functional processing by improving its signal to noise ratio.