The role of Protocadherin 9 expressing corticothalamic neurons in sensory-related behavioral performance

Sensory processing is affected in a variety of neuropsychiatric disorders. Protocadherin 9 (Pcdh9) has been implicated as a genetic risk factor for multiple psychiatric disorders, like major depressive disorder and autism spectrum disorder (ASD). It is a cell adhesion molecule involved in neuronal migration, synaptic plasticity, and circuit formation. We previously showed that Pcdh9 affects sensory cortex development and behavioral expressions related to sensory processing in a traditional knockout mouse model. To investigate the role of Pcdh9 in sensory cortex development, sensory processing, and social behavior, we generated a mouse model that only expresses Pcdh9 in corticothalamic neurons in cortex layer 6 by crossing the Pcdh9 conditional reinstatement mouse line with the Ntsr1-cre mouse model.At the moment we are performing molecular analyses to analyze Pcdh9 expression in these mice. Furthermore, multiple behavioral tests assessing a variety of sensory modalities were performed, like the bedding preference test (BPT), buried food test, olfactory habituation/dishabituation test, and prepulse inhibition test using acoustic or tactile prepulses.In the BPT, we observed that mice lacking Pcdh9 (Ntsr1-cre+/+;Pcdh9stop/stop (median=0.506, n=5)) do not have a preference for either of the two bedding materials (p=0.8). Whereas control littermates (Ntsr1-cre+/+;Pcdh9+/+ (median=0.518, n=7) and Ntsr1-creCre/+;Pcdh9+/+ (median=0.618, n=7)), and mice with reinstated Pcdh9 expression in corticothalamic neurons (Ntsr1-creCre/+;Pcdh9Re/Re (median=0.513, n=7)) do have a preference for paperchip bedding (p<0.05). Currently, we are investigating whether other sensory modalities (visual, smell, acoustic, and tactile) are affected by Pcdh9 reinstatement in corticothalamic neurons. Ultimately, these studies will contribute to our understanding of the functional relationship between early life sensory cortex development, sensory information processing, and behavior.