Lipina, Tatiana VTatiana VLipinaPrasad, TuhinaTuhinaPrasadYokomaku, DaisakuDaisakuYokomakuLuo, LinLinLuoConnor, Steven ASteven AConnorKawabe, HiroshiHiroshiKawabeWang, Yu TianYu TianWangBrose, NilsNilsBroseRoder, John CJohn CRoderCraig, Ann MarieAnn MarieCraig2017-09-072017-09-072016https://resolver.sub.uni-goettingen.de/purl?gro-2/557Calsyntenin-2 has an evolutionarily conserved role in cognition. In a human genome-wide screen, the CLSTN2 locus was associated with verbal episodic memory, and expression of human calsyntenin-2 rescues the associative learning defect in orthologous Caenorhabditis elegans mutants. Other calsyntenins promote synapse development, calsyntenin-1 selectively of excitatory synapses and calsyntenin-3 of excitatory and inhibitory synapses. We found that targeted deletion of calsyntenin-2 in mice results in a selective reduction in functional inhibitory synapses. Reduced inhibitory transmission was associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex. Clstn2(-/-) mice showed normal behavior in elevated plus maze, forced swim test, and novel object recognition assays. However, Clstn2(-/-) mice were hyperactive in the open field and showed deficits in spatial learning and memory in the Morris water maze and Barnes maze. These results confirm a function for calsyntenin-2 in cognitive performance and indicate an underlying mechanism that involves parvalbumin interneurons and aberrant inhibitory transmission.enjournal_article10.1038/npp.2015.206261717160003680841000173141741