About this Research Topic

Background

The synapse is a complex nanomachine that lies at the heart of neuronal processing. This Special Topic focuses on the functional implications of synaptic architecture. By the 1960's, important aspects of synaptic function had been established, including the requirement for presynaptic calcium entry via voltage-gated channels, releasing neurotransmitter that would then activate specialized receptors in the postsynaptic membrane, leading to postsynaptic currents. In this first era of synaptic research, electrophysiology was developing in parallel with anatomy. The morphological identification of specialized presynaptic terminals packed with small vesicles played a major role in the widespread acceptance of Katz's model of quantal transmitter release.

As already recognized by Aristotle, biological structure and function are intimately linked. Function is perhaps the more interesting scientific question, but structure is more directly answerable. In this Special Topic, we examine multiple aspects of synaptic architecture. This information constrains function, and also provides clues to aspects of synaptic function that are not yet fully understood. Conversely, some readily-accessible aspects of synaptic function provide clues to aspects of structure not yet directly visualizable.

In this work we will focus on excitatory synapses. From a strict perspective, the "synapse" perhaps only means the locus of specialized contact between a pre- and postsynaptic structure. We use the term more generally to encompass the entire region, which typically includes the presynaptic terminal, the cleft region, and the postsynaptic spine. Focusing first on structure itself, we begin with a detailed analysis at the highest resolution now available (as provided by electron tomography), then to a broader survey of the diversity of synaptic features using transmission electron microscopy, and an investigation of structural plasticity using modern tools of light microscopy. As a second part of this work, we consider the organization of specific proteins within the synaptic region, using EM for optimal resolution, and LM to permit multichannel and in vivo study; this is complemented by indirect evidence from electrophysiology. We close with modeling work that points to functional implications of structural results.

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