Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene PogZ

Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for Pogz, a high confidence autism gene. Pogz^+/- mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) is known to be necessary for normal avoidance in the EPM. We found deficient theta-frequency synchronization between the vHPC and mPFC in vivo. Furthermore, this involves a specific deficit in excitatory input from vHPC onto prefrontal GABAergic interneurons; vHPC input to mPFC pyramidal neurons remains intact. These findings illustrate how inhibitory circuit dysfunction can impair long-range communication in the context of abnormal behavior resulting from the loss of a high confidence autism gene.