In one MICrONS mouse, similar visual responses raised shared excitatory but not shared inhibitory targets of excitatory axons; the small difference passed all pre-set tests only in non-proofread axons

Question: do excitatory axons with similar visual responses converge onto inhibitory neurons, as they do onto excitatory neurons? Data: one mouse, MICrONS visual cortex (V1, RL, AL): v1300 synaptic connections, the Allen soma E/I class model and the responses of 12,894 coregistered neurons (Ding et al. 2025). Method: for 10,878 pairs of the 148 proofread functional axons, we counted shared excitatory and shared inhibitory targets and divided by the count expected from random target choice inside 50 um cubes. Poisson models related this ratio to response similarity, with soma distance, receptive-field distance, area and layer controls. A within-group permutation of functional identities (1,000) and an axon jackknife gave uncertainty. The plan was written first. Results: similar axon pairs shared more excitatory targets (+1.7% per SD of model signal correlation; permutation p = 0.018; three measures p = 0.012-0.020). Inhibitory targets showed no effect (0.4% per SD; p = 0.61; three measures p = 0.15-0.98). The inhibitory-minus-excitatory difference was negative for all three measures (permutation p = 0.003-0.036), but every jackknife interval included zero, so the primary result is uncertain. In 4,000 functional neurons with unproofread axons and local targets, the difference passed both tests for two signal-correlation measures (-0.0098, 95% CI -0.016 to -0.003, p = 0.010; -0.0074, CI -0.014 to -0.001, p = 0.005) but not for feature similarity. Without controls, inhibitory targets also had a positive association; soma proximity and area/layer explained most of it. Limitations: one animal; E/I class only, without PV, SST or VIP subclasses; 148 proofread axons; unproofread axons can have merge errors; effects are a few percent per SD.

MICrONS · functional connectomics · inhibitory interneurons · excitatory-inhibitory wiring · like-to-like connectivity · co-innervation · non-specific pooling · mouse visual cortex · electron microscopy · Allen Institute · structure-function · null result