Trans-synaptic SynCAM Interactions in the Specification of Thalamocortical Synapses

Cell adhesion proteins guide the development and maturation of neuronal connections by interacting across the synapse. Many adhesion molecules including SynCAM 1 have been implicated in Autism Spectrum Disorder (ASD) which shows sensory processing abnormalities tied to altered thalamocortical connectivity. Moreover, SynCAM 1 knockout mice present impaired thalamocortical connectivity. SynCAM 1 and -2 form transsynaptic complexes to promote excitatory synaptogenesis and synapse stabilization, yet their role in establishing thalamocortical connections is not understood. Here, we show that (1) in vivo SynCAM 1-2 interaction is more abundant than SynCAM 1-1 interaction in primary visual cortex V1. (2) SynCAM 1 and -2 expression is experience dependent as dark- reared mice had decreased SynCAM 1 and 2 (3) Silencing of SynCAM 1 at eye opening is sufficient to selectively reduce the number of thalamocortical afferents in V1 without effecting intracortical terminals and (4) ASD-linked SynCAM 1Y251S mutation destabilize the protein in silico which in turn might contribute to its interaction efficacy. Altogether, our results indicate that SynCAM 1-2 are crucial in the establishment of thalamocortical connectivity.