Impact of cGMP pathway in the peripheral and central hearing phenotype of Bdnf ^Pax2 KO mice

In previous studies using different guanylyl cyclase (GC) knock-out mouse models (NO-GC, GC-B, and GC-A KO mice), we found that GCs do not greatly interfere with basic hearing function, but rather work to maintain proper temporal sound coding, fast auditory processing, and adaptation to injury. Both acoustic trauma and age-related hearing loss result in a loss of basic hearing function and fast auditory processing. While NO-GC maintains these processes by preserving auditory nerve fibers during early life, GC-A protects against challenging conditions such as acoustic trauma or aging. To further evaluate the role of the cGMP generators NO-GC and GC-A for fast auditory processing, we analyzed a mouse model in which the fast auditory processing remains immature— Bdnf ^Pax2 KO mice. Besides the peripheral, sensory deficits in auditory processing, Bdnf ^Pax2 KO mice also exhibited impairments in central auditory function and plasticity and further presented with an autism-like behavioral phenotype. In this mouse model, we aimed to investigate if cGMP signaling, particularly via the GC-A pathway, plays a role in the aforementioned phenotype and whether it is possible to treat the peripheral and central phenotype of Bdnf ^Pax2 KO mice using cGMP enhancing drugs, such as a PDE9A inhibitor.