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

Abstract

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.

Calsyntenin-3, an atypical cadherin, suppresses inhibitory basket- and stellate-cell synapses but boosts excitatory parallel-fiber synapses in cerebellum

“…The decrease in inhibitory synapse numbers by the Clstn3 KO is consistent with previous studies suggesting that Clstn3 promotes synapse formation in the hippocampus, but these previous studies primarily identified a decrease in excitatory synapses (Kim et al, 2020; Pettem et al, 2013; Ranneva et al, 2020). We thus tested whether the Clstn3 KO also affects excitatory synapse numbers in cerebellum.…”

Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies

“…The MPFC also showed a reduction in the length of perforated synapses as well as in the width of the synaptic cleft PSD, presenting a surprisingly increased number of synaptic vesicles. In contrast, the presynaptic area of the hippocampal neurons was not changed in Clstn2 knockout mice, but the number of synaptic vesicles was significantly reduced [142].…”

Whole‐genome sequencing reveals new Alzheimer's disease–associated rare variants in loci related to synaptic function and neuronal development

“… 56 CLSTN2 encodes Calsyntenin 2, which modulates calcium‐mediated postsynaptic signaling in the brain. Absence of CLSTN2 impairs synaptic complexes in mice, 57 and has been associated with episodic memory function in human subjects. 58 …”