Vocal and physical phenotypes of calsyntenin2 knockout mouse pups model early-life symptoms of the autism spectrum disorder.

This study discovered a novel acoustic phenotype in Calsyntenin2 deficient knockout (Clstn2-KO) pups in the neurodevelopment period of 5-9 postnatal days (PND 5-9). The narrowband ultrasonic calls (nUSVs) were less complex (mostly one-note, shorter in duration and higher in peak frequency) in Clsnt2-KO than in wild-type (WT) C57BL/6 J pups. The wideband ultrasonic calls (wUSVs) were produced substantially more often by Clstn2-KO than WT pups. The clicks were longer in duration and higher in peak frequency and power quartiles in Clstn2-KO pups. The elevated discomfort due to additional two-minute maternal separation coupled with experimenter's touch, resulted in significantly higher call rates of both nUSVs and clicks in pups of both genotypes and sexes compared to the previous two-minute maternal separation, whereas the call rate of wUSVs was not affected. In Clstn2-KO pups, the prevalence of emission of wUSVs retained at both sex and both degrees of discomfort, thus providing a reliable quantitative acoustic indicator for this genetic line. Besides the acoustic differences, we also detected the increased head-to-body ratio in Clstn2-KO pups. Altogether, this study demonstrated that lack of such synaptic adhesion protein as calsyntenin2 affects neurodevelopment of vocalization in a mouse as a model organism.

Lack of synaptic protein, calsyntenin-2, impairs morphology of synaptic complexes in mice.

Calsyntenin-2 (Clstn2) is the synaptic protein, which belongs to the superfamily of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons, associated with hyperactivity, deficient spatial memory, and social behavior. Therefore, we sought to characterize morphometric features of the ultrastructure of synaptic complexes of hippocampal and cortical neurons in Clstn2-KO mice, using high magnification electron microscopy. Morphometric analysis revealed a reduction of symmetric (inhibitory) synaptic density, length of synaptic contacts, and postsynaptic density in neurons of Clstn2-KO mice. Moreover, cortical neurons of Clstn2-KO mice were characterized by the predominance of the simplified type of synapses with the emergence of negative curvature of the synaptic zone in Clstn2-KO mice. Notably, presynaptic zones of cortical neurons of Clstn2-KO mice were characterized by the increased number of synaptic vesicles in opposite to the decreased number of synaptic vesicles in the presynaptic zones of hippocampal neurons. Overall, we found that lack of calsyntenin-2 leads to the striking architectonic alterations of synaptic complexes in the mouse brain, disrupting synaptic density, shape, and connectivity.