Study Of The Role Of Primary Cilia In Interneurons Using Knockout Mouse Model

Primary cilium is a very short filiform structure locating on the surface of various somatic cells.In sensory neurons of the visual,auditory,and olfactory system,primary cilia have long been recongnized as the location of sensory stimulus reception.During early development of the nervous system,primary cilia of neural stem cells mediate the signal transduction of morphagens including Shh and Wnt.In recent years,emerging studies have indicated other important functions of the primary cilia in somatic cells.The "ciliopathies",a group of genetic disorders caused by defects in primary ciliary,are characterized by pleiotropic clinical features and are associated with distinctive developmental or degenerative phenotypes in different tissues.Although more than fifty ciliopathy-related genes have identified,the detailed underlying signaling mechanisms are not clear.A major population of interneurons in the forebrain is the Parvalbumin-expressing neurons,whose misfunction is relevant to multiple psychiatric disorders.In this study,we specifically knocked out the primary cilia in parvalbumin-expressing(PV+)interneuron of C57/BL6 mice using the Cre-LoxP conditional recombination system,and examined its influence on the animal behavior in order to understand the physiological role of cilia in interneurons.1)Immunofluorescent staining showed that PV+ interneurons broadly distribute in the cortex,primary visual cortex,striatum,hippocampus,external cortex of the inferior colliculus and cerebellum.Significant reduction in the density of primary cilia was observed in PV-Cre::Ift88flox conditional knockout mice.2)Behavioral tests showed a higher locomotor activity and lower anxiety level of cilia knockout mice,with a sex difference in severity.In summary,primary cilia knockout in PV+ interneuron caused emotional changes in mice.In view of the function of forebrain interneurons,we speculate that misfunction of PV+ interneurons distributing in the prefrontal cortex and the striatum may be responsible to the emotional change of knockout mice.