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Ju Lu and Jeff Lichtman

It is widely believed that in order to understand how the nervous system works, one needs to know where neural processes go and with which cells they connect. Conventionally, this kind of information is obtained by labeling a small number of neurons from one sample and then pooling data from multiple samples in order to infer the organization of the complete circuit.

However, this approach is not useful if there is significant variation from sample to sample. In this work an alternative approach was attempted: obtain the complete wiring diagram (connectome) of a circuit by tracing out all the processes in one sample. Confocal microscopy was used in transgenic mice that express fluorescent protein in motor neurons to generate tens of thousands of images of axons that innervate a small ear muscle. These images were analyzed with semi-automated tracing tools to get the full wiring diagram.

Comparison of each neuron and its counterpart on the opposite side of the animal revealed that each connectome was unique. Furthermore axonal arbors appeared to be much longer than expected from the well known hypothesis that wiring length of axons should be minimized. Thus mammalian muscle function is implemented with a variety of wiring diagrams that differ substantially in anatomical form, even within a common genetic background. This result suggests that in mammals the structure of the nervous system is unfettered from strict genetic determinism.


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