CDKL5 Deficiency Disorder (CDD)  is a neurodevelopmental condition affecting predominantly females with an incidence of 1:40,000/60,000.  Clinical features of CDD include developmental delays, hypotonia, deficits in learning, memory, and social behaviors, and most notably seizure onset before the age of 3 months. CDD is caused by mutations in the X-linked gene Cyclin-Dependent Kinase-Like  5 (CDKL5). It encodes a Serine/Threonine kinase that implicates neuronal migration, axon outgrowth, dendritic morphogenesis, and synapse development.

How interneurons are affected remains unknown. In this project, our goal is to investigate how CDKL5 dysfunction impairs interneuron development. We used a conditional KO mouse model to examine how the deletion of CDKL5 in excitatory neurons changes the density of Somatostatin (SST+) interneurons in the hippocampus and medial prefrontal cortex. We found that early knockout of CDKL5 in excitatory neurons can increase interneuron density in the hippocampus and medial prefrontal cortex. SST+ interneurons are involved in feedback inhibition, which maintains the balance between excitatory and inhibitory neurons. An imbalance could lead to seizures like in CDD.