Corticothalamic processing across the neuropsychiatric spectrum: The role of protocadherin 9 expression in different sensory modalities

Our perception of and response to our environment depends on internal processing of external information. For example, to interpret a person's mood, it is important to integrate facial expression, voice intonation and body language, among other things. Thus, the interpretation of social cues requires a high level of sensory integration. For this to proceed smoothly, the neuronal networks involved in sensory processing must be correctly developed. However, in many neuropsychiatric disorders, the underlying mechanisms of these processes are altered. We found that sensory processing in several senses (smell, sight, touch and hearing) is impaired in mice lacking the risk gene Pcdh9. Many of these deficiencies could be partially or completely restored by restoring protein expression of Pcdh9 in corticothalamic (CT) neurons in cortical layer 6 (ctx6). This was the case for smell, vision and touch but not for hearing. In addition, we found that in the absence of Pcdh9, mice exhibit long-term social discrimination deficits. This social phenotype could not be overcome by restoring Pcdh9 expression in only the ctx6 CT neurons.
In summary, the work described in this thesis highlights the importance of Pcdh9 in the formation of sensory networks early in life and sensory processing in multiple senses later in life. Furthermore, these findings underscore that Pcdh9 expression in ctx6 CT neurons plays an essential role in sensory networks, and that restoration of Pcdh9 in these neurons can (partially) restore some of the phenotypes seen in various senses.