The cell-adhesion code that underlies the molecular logic of synapse formation

The brain processes information in millions of neural circuits that operate in parallel or in an interleaved fashion. Neural circuits in turn process information by transmitting and computing signals at synapses. Neural circuit computations critically depend not only on the number and location of synapses between the neurons, but also on the properties of these synapses that can exhibit a wide range of reliability and plasticity. We hypothesize that the construction of neural circuits, mediated by formation of defined synapses, is based on a molecular logic which can serve to explain unitary principles by which the brain processes information. Moreover, we posit that the number, location, and properties of synapses are determined by interactions between pre- and postsynaptic recognition and signaling molecules, and we thus refer to the rules by which these molecules construct circuits as the molecular logic of neural circuits. Several cell-surface and signaling molecules contributing to the molecular logic of neural circuits have been characterized. Two types of complexes mediating trans-synaptic interactions that control the architecture of synapses stand out: Presynaptic neurexin adhesion molecules and their multifarious postsynaptic ligands, including neuroligins and cerebellins, and postsynaptic latrophilins and Bai’s, which are adhesion-GPCRs that interact with presynaptic ligands in synapse formation. In my lecture, I will describe recent progress in understanding how selected trans-synaptic interactions guide and shape the formation of synapses.