Resolving presynaptic structure by electron tomography.

A key goal in neurobiology is to generate a theoretical framework that merges structural, physiological, and molecular explanations of brain function. These categories of explanation do not advance in synchrony; advances in one category define new experiments in other categories. For example, the synapse was defined physiologically and biochemically before it was visualized using electron microscopy.

Synaptic inputs compete during rapid formation of the calyx of Held: a new model system for neural development.

Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics.