Nobel Laureate Lecture: The Molecular Architecture of Synapse Formation

Abstract:

The brain processes information via signals that are processed in a vast number of neural circuits that operate in a parallel, interleaved, or sequential fashion. In each neural circuit, information transmitted from one neuron to the next at synapses that computationally process the information as it is being transmitted, translating a presynaptic spike code into distinct postsynaptic signals depending on the properties of the synapses.

Information processing by neural circuits critically depend on the number and location of synapses between their constituent neurons and equally on the computational properties of these synapses that vary greatly.

We posit that the synaptic architecture of neural circuits is based on a molecular logic that governs the establishment and functional specification of synapses. Moreover, we posit that this molecular logic is controlled by transsynaptic adhesion complexes formed between pre- and postsynaptic recognition and signaling molecules.

Multiple 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 signaling partners, including neuroligins and cerebellins, and postsynaptic latrophilins and Bai’s that act as adhesion-GPCRs and interact with presynaptic ligands, including teneurins and RTN4Rs, 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 and thereby control the molecular logic of neural circuits. I will focus on only a few example given the amount of material available but encourage the audience to access our publications for more information.