Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins.

Presynaptic neurexins are key regulators of synapse properties that arguably represent the best-studied synaptic adhesion molecules. Despite thousands of papers, however, no direct comparison of overall neurexin functions in different types of synapses is available. A decade ago, we provided such an analysis but we recently retracted this paper because four images contained microduplications that, although without discernible impact on the paper's conclusions, could not be corrected. As a result, the scientific community lost access to primary data that established the fundamental principle that neurexins perform profoundly different functions in different types of synapses. In the present study, we have therefore reanalyzed the original raw data and expanded their conclusions with new experiments to document, in a single study, the basic contributions of neurexins to different synapses. We used triple conditional knockout mice targeting all neurexins except for Neurexin-1γ and applied neuron-specific manipulations combined with slice electrophysiology, two-photon Ca Significance Statement: Neurexins are abundant presynaptic adhesion molecules expressed from three genes in thousands of splice variants. Although neurexins are well studied, no analysis that compares neurexin deletions in multiple types of synapses is currently available. Here, we provide such an analysis by examining triple conditional knockout mice that delete all neurexins except for Neurexin-1γ. Using neuron-specific manipulations combined with slice electrophysiology, two-photon Ca