In vivo imaging demonstrates dendritic spine stabilization by SynCAM 1

Abstract

Formation and stability of synapses are required for proper brain function. While it is well established that synaptic adhesion molecules are important regulators of synapse formation, their specific role during different phases of synapse development remains unclear. To investigate the function of the synaptic cell adhesion molecule SynCAM 1 in the formation, stability, and maintenance of spines we used 2-photon in vivo imaging to follow individual spines over a long period of time. In SynCAM 1 knockout mice the survival rate of existing spines was reduced and fewer filopodia-like structures were converted into stable spines. SynCAM 1flag overexpression resulted in more stable spines and fewer filopodia-like structures. When SynCAM 1flag overexpression is turned on the spine density rapidly increases within a few days. Interestingly, the spine density stayed at an elevated level when SynCAM 1flag overexpression was turned off. Our data indicate that the SynCAM 1 induced altered spine density is not caused by the formation of newly emerging protrusions, instead SynCAM 1 stabilizes nascent synaptic contacts which promotes their maturation. Concomitant with the synaptic stabilization, SynCAM 1 generally prolongs the lifetime of spines. In summary, we demonstrate that SynCAM 1 is a key regulator of spine stability.

The fate of hippocampal synapses depends on the sequence of plasticity-inducing events

“…The mechanism linking LTP to synaptic stabilization, and LTD to destabilization, is likely to involve several processes. Synaptic tenacity is known to be affected by trans-synaptic proteins such as Neuroligin-1 and SynCAM-1 ( Zeidan and Ziv, 2012 ; Körber and Stein, 2016 ), PSD-95 ( De Roo et al, 2008 ; Cane et al, 2014 ), ubiquitin protein ligase E3A ( Kim et al, 2016 ), ensheathment of the synapse by astrocyte processes ( Bernardinelli et al, 2014 ) and many other local factors. It may be a combination of local physical changes and distributed network effects, such as the recurrent reactivation of a specific circuit ( Wei and Koulakov, 2014 ; Novitskaya et al, 2016 ), which makes once potentiated synapses robust against depression ( Figure 5B ) and pruning ( Figure 3E ).…”

MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density

“…In addition to their role in other tissues, SynCAMs are known synaptic cell adhesion molecules: through homophilic and heterophilic interactions between their extracellular domains, these molecules form trans-synaptic complexes 30 31 , and it has been demonstrated that these complexes are involved in synaptogenesis (for review see ref. 32 ) and also in synapse stabilisation 33 34 .…”

Transcellular Nanoalignment of Synaptic Function

“…In terms of physiological maturation, neurexins are critical synaptic organizers as first shown in vivo by the result that α-neurexin loss impairs evoked neurotransmission (Missler et al, 2003). Additional evidence for instructive roles of trans-synaptic organizers in synapse development comes from studies of another class of postsynaptic neurexin ligands called LRRTM proteins (de Wit and Ghosh, 2016), LAR phosphotyrosine phosphatases that signal on the presynaptic side (Takahashi and Craig, 2013), and SynCAM 1, which is preferentially postsynaptic and required and sufficient to control the number of excitatory synapses in vivo (Park et al, 2016; Korber and Stein, 2016; Robbins et al, 2010). The subsynaptic functions of these and other adhesion molecules could include localization or retention of pre- and post-synaptic nanodomains at developing and mature synapses, altering the geometry of the cleft and hence the diffusion of neurotransmitters, or modulating presynaptic Ca channel function (Freche et al, 2011; Glebov et al, 2016; Tong et al, 2017; Wahl et al, 1996).…”