Abstract
SUMMARYReciprocal synapses are formed by neighboring dendritic processes that create the smallest possible neural circuit. Reciprocal synapses are widespread in brain and essential for information processing, but constitute a conceptual conundrum: How are adjacent pre- and post-synaptic specializations maintained as separate functional units? Here, we reveal an organizational principle for reciprocal synapses, using dendrodendritic synapses between mitral and granule cells in the mouse olfactory bulb as a paradigm. We show that mitral cells secrete cerebellin-1 to block the cis-interaction of mitral cell neurexins with neuroligins, thereby enabling their separate trans-interactions. Ablating either cerebellin-1 or neuroligins in mitral cells severely impaired granule cell→mitral cell synapses, as did overexpression of postsynaptic neurexins that form cis-complexes with neuroligins, but not of mutant neurexins unable to bind to neuroligins. Our data uncover a cis/trans-protein interaction network as a general design principle that organizes reciprocal dendro-dendritic synapses by compartmentalizing neurexin-based trans-synaptic protein complexes.
Publisher
Cold Spring Harbor Laboratory