Although the prefrontal cortex (PFC) has been strongly implicated in social interactions, the means by which social information is encoded in populations of PFC neurons is not well understood. A new study provides new insight into how ensembles of PFC neurons are tuned to social cues and how this response is different in mice lacking Cntnap2, a strong candidate autism spectrum disorder risk gene.

The work was supported in part by a Research Award to SFARI Investigator Ofer Yizhar. The authors developed a custom-built odor delivery system, which allowed precise delivery of both social and nonsocial odors while recording medial PFC activity in freely behaving mice. They found that, in wild-type mice, individual units in the medial PFC responded more strongly to social odors (from other mice) than nonsocial odors, which was also manifest in the differential firing rate and distinct encoding distributions of populations of neurons. When they examined Cntnap2-null mice, their clear lack of preference for social stimuli was reflected at the level of individual units and in the lack of category-level separation observed when recording population-level neuronal activity. Moreover, the mutant mice did not show the kind of experience-dependent refinement of neuronal activity in response to repeated exposures that was observed in wild-type mice, where there was increased separation in the pattern of activity between social and nonsocial odors.

Finally, Yizhar and colleagues reported increased spiking irregularity (neural noise) in the Cntnap2-null mice, which correlated with their deficits in social processing. They suggest that this neural noise may have an important role in the failure of the mutant mice to appropriately encode and respond to social cues.