In mouse V1, distance-matched EM wiring predicted slice connection rates of excitatory inputs to interneurons and of Pvalb-like outputs within 20%, but not of inhibition onto interneurons

Question: at matched soma distance, does electron microscopy (EM) wiring predict the connection rates that paired recordings detect in mouse V1 slices? Data: MICrONS minnie65 v1300 (one mouse; 75 extended excitatory and 98 proofread inhibitory axons; inhibitory axons put in perisomatic, distal and interneuron-targeting groups as Pvalb-, Sst- and Vip-like) and Allen Synaptic Physiology r2.1 (21,958 probed mouse V1 pairs, 2,171 slices). Method: ratio R of observed physiology connections to EM-expected connections in 25 um distance bins, per class pair (22 pairs); bootstrap over EM axons and slices; tests of distance, slice depth, virtual slicing of EM synapses, and synapse location and size. Results: excitatory inputs to Pvalb, Sst and Vip cells agreed (R 1.06, 0.80, 1.05) and Pvalb to excitatory gave R 0.80 (0.69 to 0.95). Excitatory to excitatory gave R 1.47 (1.24 to 1.79), 1.23 for the more complete half of EM axons, which is consistent with incomplete EM axons. Sst to excitatory gave 0.46. Inhibitory connections onto interneurons gave R 0.09 to 0.74 in all nine class pairs (Sst to Sst 0.09, Vip to Vip 0.09). R did not fall with distance (except excitatory to Pvalb) and had no clear slice-depth term; virtual slicing removed only about 10 percent of EM connections at the median recorded depth of 71 um. EM synapse distance from the target soma and synapse size did not explain the inhibitory differences; target class did. Limitations: one EM animal, 20 to 37 source axons per class, EM groups are not Cre classes, approximate EM layers, different ages and protocols, and an excitatory axon-status criterion chosen after inspection of output counts.

connectomics · MICrONS · Allen Synaptic Physiology · connection probability · paired recordings · interneurons · slice truncation · mouse visual cortex · structure-function · electron microscopy