Moritz Helmstädter (Structure of Neocortical Circuits Group, Max Planck Institute of Neurobiology, Munich)
Dense reconstruction of neuronal circuits
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Philippstr. 13, Haus 6
The mapping of neuronal connectivity is one of the main challenges in neuroscience. Only with the knowledge of wiring diagrams is it possible to understand the computational capacities of neuronal networks, both in the sensory periphery, and especially in the cerebral cortex. Statistical circuit mapping using a combination of paired intracellular recordings and anatomical reconstructions have provided insight into the connectivity between populations of cells, as will be exemplified for the translaminar circuits involving inhibition in a cortical column of primary somatosensory cortex. To move beyond pairwise connectivity statistics, however, dense circuit mapping is required. One approach for dense circuit mapping is based on 3-dimensional electron microscopy (EM) imaging of tissue, which allows the tissue to be imaged at nanometer-scale resolution across substantial volumes (typically hundreds of micrometers per spatial dimension) using Serial Block-Face Scanning Electron Microscopy (SBEM). The most time-consuming aspect of circuit mapping, however, is image analysis; analysis time far exceeds the time needed to acquire the data. Therefore, we developed methods to make circuit reconstruction feasible by increasing analysis speed and accuracy, using a combination of crowd sourcing and machine learning. We have applied these methods to circuits in the mouse retina, mapping the complete connectivity graph between hundreds of neurons, and we are currently improving these methods for application to neocortical circuits.
Helmstaedter M, Staiger JF, Sakmann B, Feldmeyer D (2008) Efficient recruitment of layer 2/3 interneurons by layer 4 input in single columns of rat somatosensory cortex. J Neurosci 28:8273-8284.
Briggman KL, Helmstaedter M, Denk W (2011) Wiring specificity in the direction-selectivity circuit of the retina. Nature 471:183-188.
Helmstaedter M, Briggman KL, Denk W (2011) High-accuracy neurite reconstruction for high-throughput neuroanatomy. Nat Neurosci 14:1081-1088.