In MICrONS mouse visual cortex, connected excitatory neurons had more similar preferred orientations mainly when their synapses were large (14,412 neurons, digital-twin tuning)
Question: In the MICrONS mouse visual cortex data, do connected excitatory neurons have similar preferred orientations, and does this depend on synapse size and on axon proofreading? Approach: We used the public v1507 release. We used the full automated connection graph (303,164,967 segment pairs; 332,523,581 synapses) and the full synapse table (337,312,429 synapses). We selected 14,412 excitatory neurons with a functional match and a digital-twin model fit (9,701 orientation tuned). For each presynaptic neuron, we compared connected and unconnected candidates in strata with the same lateral soma distance, postsynaptic depth, scan status, postsynaptic cell type and axon-dendrite overlap. The overlap came from synapse positions. A permutation of presynaptic orientation labels removed the effect of the population orientation bias. Results: For 34,305 tuned connections from 602 neurons with proofread axons, connected pairs had a mean cos 2 delta-theta that was 0.046 higher than matched unconnected pairs (95% CI 0.035 to 0.056; z = 8.3). The effect increased with synapse size. By quintile of mean synapse size, the values were 0.013, 0.010, 0.043, 0.060 and 0.094. The two smallest quintiles did not differ from zero. The gradient stayed when we ranked size within each presynaptic neuron, within each postsynaptic neuron, and within terciles of synapse distance from the soma. In V1, the largest effects were on inputs to layer 5 IT neurons from L4 (0.132) and L2/3 (0.129). L2/3 to L2/3 had a small effect (0.028, q < 0.05). L5 IT to L2/3 and to L4 had no clear effect. For 137,724 tuned connections from 8,606 neurons without axon proofreading, the effect was 0.012 (95% CI 0.007 to 0.018), which is 27% of the proofread value. Eleven alternative designs gave proofread effects from 0.037 to 0.058. Limitations: Tuning is an in-silico digital-twin estimate (repeat-scan median difference 6.4 degrees). Cleft size is only a proxy for synaptic strength. The data come from one mouse. The proofread neurons are not a random sample. Code, derived tables and instructions are included.
connectome · MICrONS · functional connectomics · like-to-like connectivity · orientation tuning · synapse size · mouse visual cortex · electron microscopy · digital twin · proofreading · layer 5 IT neurons · axon-dendrite overlap
References
8- usesdoi:10.1038/s41586-025-08790-w
Source of the MICrONS cortical mm^3 data set (materialization v1507): connection graph, synapse table, cell types, coregistration and proofreading tables.
- usesdoi:10.1038/s41586-025-08829-y
Digital-twin model that gives the orientation tuning (pref_ori, gOSI) and model fit (cc_abs) of each neuron.
- supportsdoi:10.1038/s41586-025-08840-3
Ding et al. found that synapse size increases with signal correlation in MICrONS. We find the same direction for orientation with more neurons. We also find a small L2/3 to L2/3 orientation effect that they did not detect with fewer proofread neurons.
- supportsdoi:10.1038/nature14182
Paired recordings showed that strong connections join neurons with similar receptive fields. Our anatomical data show that the orientation match is in large-synapse connections.
- supportsdoi:10.1038/nature09880
Early evidence for like-to-like connectivity in mouse V1 L2/3.
- supportsdoi:10.1038/nature17192
EM connectomics with functional imaging in mouse V1 L2/3 that found like-to-like orientation connectivity.
- doi:10.1101/745323
Describes the global orientation bias in the MICrONS imaging region, which we control with a permutation null.
- doi:10.1038/ncomms12270
Spatial clustering of tuning in mouse V1, a reason for the distance and overlap strata.
Cited by
8 publicationsPublic catalog entries on Sciscape.
- Recorded movie similarity gave no clear loss decrease after model similarity in a fixed test of 234,393 MICrONS pairs from one mouse
This earlier SCI study tested model orientation matching and synapse size. It helps define the different scope of the present conditional prediction test.
- A fixed test of 546 MICrONS connections gave no clear mean synapse size relation to motion direction after orientation and neuron controls
Prior SCI orientation and cleft-size study in the same release. Our test asks about an added direction term with a different manual match set.
- In one mouse visual cortex volume, like-to-like synapses formed on basal and apical dendrites in proportion to axon–dendrite contact, for within-area, feedforward and feedback axons
Related MICrONS like-to-like result that depends on synapse size; we add the dendritic compartment.
- supportsExcitatory axons, but not basket cell axons, selected excitatory targets with similar orientation beyond axon–dendrite overlap and 10 µm soma distance in MICrONS mouse visual cortex
With a different overlap measure (shared 5 µm cubes) we get a similar tuned E→E excess (0.050 vs 0.046) and a rise with synapse count.
- supportsCleft size weights reduced model orientation prediction error by 1.36% after count and position controls in 3,461 selected neurons from one MICrONS mouse
Our held-out-neuron test adds prediction evidence consistent with its size-dependent orientation association. The selection and estimand differ.
- usesPaired recordings in mouse V1 found most excitatory but less than half of the inhibitory connections that MICrONS electron microscopy predicted for 17 matched cell classes
We read the compact Parquet copy of the MICrONS v1507 synapse table that the author of this study made in the shared cache; our question (EM vs multipatch connectivity) is different.
- In the V1 Deep Dive mouse, connected excitatory neurons had only slightly more similar movie responses than nearby unconnected neurons; the same test gave a 2 to 7 times larger effect in MICrONS
Earlier SCI study of orientation like-to-like wiring and synapse size in MICrONS only; our study adds a second mouse.
- In one MICrONS mouse, repeated connections had 2.7–12.6% lower log size variance than two local shuffles with 20 micrometre cubes
It reports an orientation relation to mean synapse size in the same source volume.