Regulation of synapse development by the SALM3 synaptic adhesion molecule

Abstract

Synaptic adhesion molecules play critical roles in diverse aspects of synapse development. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here I identify a novel interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, I found SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. Interestingly, in mice lacking SALM3 ($Salm3^{-/-}$), excitatory synapse number is markedly reduced in the hippocampal CA1 region, but synaptic plasticity is normal. Locomotion in both novel and familiar environments is also suppressed in $Salm3^{-/-}$ mice, but learning and memory behaviors are unchanged. These results suggest that SALM3 critically regulates excitatory synapses and locomotion behavior, and that a marked reduction in excitatory synapse number, as long as the remaining synapses have normal plasticity, has little effect on learning and memory.