Abstract
Calsyntenin-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.
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We thank Nazarine Fernandes for excellent technical assistance and Konstantin Pavlov for skillful assistance with EthoVision.
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Lipina, T., Prasad, T., Yokomaku, D. et al. Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission. Neuropsychopharmacol 41, 802–810 (2016). https://doi.org/10.1038/npp.2015.206
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DOI: https://doi.org/10.1038/npp.2015.206
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