Cre-line neuromodulatory axon density did not explain regional running modulation of visual spiking in two Allen Neuropixels mouse cohorts; a VTA dopamine-line association depended on two regions

Question: does the density of cell-type-specific neuromodulatory axons in a mouse brain region predict how much running changes visual responses there? Approach: we used the AllenSDK running-modulation index of units in two independent Allen Visual Coding Neuropixels cohorts (26 and 26 mice with locations; 35-42 regions in visual cortex area x layer, thalamus, hippocampal formation, midbrain) and region effects with mouse fixed effects. We compared them with projection-density maps from 58 Allen Mouse Connectivity experiments: noradrenaline (LC), acetylcholine (basal forebrain; PPN/LDT), serotonin (DR), dopamine (VTA), histamine (TMN) and motor cortex (MOs, ACA). Tests used within-division partial correlation, injection-distance control, within-division permutation, and fit-on-one-cohort, test-on-the-other prediction. Results: the regional profile reproduced between cohorts (r = 0.61 for gratings; 0.55 within divisions) but not inside visual cortex (r = -0.10). The pre-stated positive noradrenaline and basal-forebrain acetylcholine relations were not found (gratings partial r -0.18 and +0.18 pooled, p > 0.2); noradrenaline was negative in all nine tests and significant only for flashes. The VTA dopamine-line map was negative in both cohorts (r = -0.47, -0.57; Holm p 0.13, 0.09) and predicted the other cohort, but without DG and MGd r = -0.15. Limitations: few regions, coarse tracer density with passing fibres, injections in other mice, and a coarse running index.

neuromodulation · locomotion · running modulation · Allen Visual Coding Neuropixels · Allen Mouse Connectivity Atlas · Cre-line tracing · noradrenaline · acetylcholine · dopamine · structure-function · replication across cohorts · null result