Towards Semi-Automatic Reconstruction of Neural Circuits
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The spatial layout of neuronal arbors and their synapses in the brain, also known as the wiring diagram or the connectome,1 may provide the basis for formulating experimentally testable hypotheses of neural circuit function. In the brain, the small dimensions of terminal dendrites and synapses, and the anatomical flexibility of neuronal arbors implementing the same function in the brains of two different individuals, conspire against the standard scientific approach of examining a small piece of tissue and generalizing to the rest. Furthermore, the identification of the synaptic contacts between neurons is not sufficient to capture important aspects of circuitry function such as neuromodulation,2which operates via volume release and difusion through the extracellular space. To obtain a connectome complete with spatial information, scientists must image the brain at nanometer resolution and reconstruct neuronal arbors, synapses, and glial cells. So far, only electron microscopy (EM)...