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.