The Interscutularis Muscle Connectome

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Abstract
The complete connectional map (connectome) of a neural circuit is essential for understanding its structure and function. Such maps have only been obtained in Caenorhabditis elegans. As an attempt at solving mammalian circuits, we reconstructed the connectomes of six interscutularis muscles from adult transgenic mice expressing fluorescent proteins in all motor axons. The reconstruction revealed several organizational principles of the neuromuscular circuit. First, the connectomes demonstrate the anatomical basis of the graded tensions in the size principle. Second, they reveal a robust quantitative relationship between axonal caliber, length, and synapse number. Third, they permit a direct comparison of the same neuron on the left and right sides of the same vertebrate animal, and reveal significant structural variations among such neurons, which contrast with the stereotypy of identified neurons in invertebrates. Finally, the wiring length of axons is often longer than necessary, contrary to the widely held view that neural wiring length should be minimized. These results show that mammalian muscle function is implemented with a variety of wiring diagrams that share certain global features but differ substantially in anatomical form. This variability may arise from the dominant role of synaptic competition in establishing the final circuit. Conventionally, the organization of a neural circuit is studied by sparsely labeling its constituent neurons and pooling data from multiple samples. If significant variation exists among circuits, this approach may not answer how each neuron integrates into the circuit's functional organization. An alternative is to solve the complete wiring diagram (connectome) of each instantiation of the circuit, which would enable the identification and characterization of each neuron and its relationship with all others. We obtained six connectomes from the same muscle in adult transgenic mice expressing fluorescent protein in motor axons. Certain quantitative features were found to be common to each connectome, but the branching structure of each axon was unique, including the left and right copies of the same neuron in the same animal. We also found that axonal arbor length is often not minimized, contrary to expectation. Thus mammalian muscle function is implemented with a variety of wiring diagrams that share certain global features but differ substantially in anatomical form, even within a common genetic background.