A Subtype-Specific Function for the Extracellular Domain of Neuroligin 1 in Hippocampal LTP

At neuronal excitatory synapses, two major subtypes of the synaptic adhesion molecule neuroligin are present. These subtypes, neuroligin 1 and neuroligin 3, have roles in synaptogenesis and synaptic maintenance that appear largely overlapping. In this study, we combine electrophysiology with molecular deletion and replacement of these proteins to identify similarities and differences between these subtypes. In doing so, we identify a subtype-specific role in LTP for neuroligin 1 in young CA1, which persists into adulthood in the dentate gyrus. As neuroligin 3 showed no requirement for LTP, we constructed chimeric proteins of the two excitatory neuroligin subtypes to identify the molecular determinants particular to the unique function of neuroligin 1. Using in vivo molecular replacement experiments, we find that these unique functions depend on a region in its extracellular domain containing the B site splice insertion previously shown to determine specificity of neurexin binding. ► NLGN1, but not NLGN3, is required for LTP in adult dentate gyrus ► NLGN1 is also required for LTP in young CA1 ► The difference between NLGN1 and NLGN3 is due to unique extracellular domains ► Only chimeric neuroligins containing the B site insertion rescue LTP Neuroligins comprise a family of postsynaptic cellular adhesion molecules. Shipman and Nicoll identify a specific role for one splice variant of neuroligin 1 in the support of hippocampal LTP during development.