Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A ) Timeline of chronic recordings. ( B ) Imaging and stimulation setups. Widefield and two-photon imaging was performed on the implanted hemisphere, and visual stimulation was applied to the contralateral eye. ( C ) Example widefield images of neural (Ca 2+ dF/F 0 ) and OEF hemodynamic responses induced by 25-Hz ICMS. Scale bar = 500 µm. ( D and E ) Time course (left) and distance profile (right; measured at 5 [red] and 20 [blue] seconds after stimulation onset) of induced neural (D) and hemodynamic (E) responses. Mean ± SD across four trials. Shaded bar indicates stimulation period (0-10 s); vertical dashed lines mark the time points of distance profiles.

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques: Imaging

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A ) Coefficient of variation (CV, pixel-wise standard deviation normalized by mean over time) of widefield Ca 2+ (i) and hemodynamics (ii) during pre-stimulation periods at day 0 (top) and day 14 (bottom). ( B ) CV (top) and silencing index relative to 350 µm (SI 350 = [CV d -CV 350 ]/CV 350 , where d = 50, 150, 250, 350, or 450 μm) during pre-stimulation periods (bottom) across distances and imaging days. ( C ) CV map during visual stimulation. ( D ) CV and SI 350 during visual stimulation. * in SI 350 plots indicate significant differences from 0 (one-sample t-test with Bonferroni correction, p < 0.05; colors correspond to days after implantation).

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques: Standard Deviation, Imaging

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A-C ) Example colormaps from a single mouse showing Ca 2+ responses during ( A ) 25-Hz ICMS, ( B ) 250-Hz ICMS, and ( C ) visual stimulation at (i and ii) day 0 and (iii and iv) day 21. Only increases from pre-stimulation baseline are shown in red. Corresponding time courses within 500 µm from the stimulation site are shown in (v) (mean ± SD across 4 trials). ( D-F ) Chronic comparisons of Ca 2+ activation magnitude (D), spatial spread (E), and duration (F) across days post-insertion. Mean ± SEM across mice. * next to line plot indicates a significant effect of day (LME model).

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques: Activation Assay

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A ) Example Ca 2+ response images at days 0 and 7 under (i) 25-Hz ICMS, (ii) 250-Hz ICMS, and (iii) visual stimulation. Corresponding time courses are shown in (iv; mean ± SEM across cells for soma, mean ± SEM across repeats for neuropil; scale bars = 5 s and 5%). ( B and C ) Chronic comparisons of somatic activation magnitudes (B) and durations (C). ( D and E ) Somatic depression magnitude (D) and duration (E) across days. ( F and G ) Neuropil activation magnitude (F) and duration (G) across days. ( H and I ) Neuropil depression magnitude (H) and duration (I) across days. Mean ± SEM across cells (B-E) or mice (F-I); “<“ and “>“ indicate significant differences compared with days 0 and 84, respectively (LME model followed by Welch’s t-test with Holm-Bonferroni correction).

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques: Activation Assay

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A-C ) Example colormaps of a single mouse showing Ca 2+ responses after ( A ) 25-Hz ICMS, ( B ) 250-Hz ICMS, and ( C ) visual stimulation at (i and ii) day 0 and (iii and iv) day 21. Only decreases from pre-stimulation baseline are shown in blue; darker blue indicates stronger depression. Corresponding time courses within 500 µm from the stimulation site are shown in (v) (mean ± SD across 4 trials). Traces during the stimulation period (0-10 s) are omitted for clarity. ( D-F ) Chronic comparisons of Ca 2+ depression magnitude (D), spatial spread (E), and duration (F) across days post-insertion. Mean ± SEM across mice.

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques:

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A-C ) Example OEF response colormaps from a single mouse during and after ( A ) 25-Hz ICMS, ( B ) 250-Hz ICMS, and ( C ) visual stimulation at (i and ii) day 0 and (iii and iv) day 21. Corresponding time courses within 500 µm of the stimulation site are shown in (v; mean ± SD across 4 trials). OEF represents deoxyhemoglobin relative to total hemoglobin (see 2.4.4), where decreases from baseline (0.25) indicate relative increases in oxyhemoglobin, reflecting enhanced metabolic supply. ( D-F ) Chronic comparisons of OEF magnitude (D), spatial spread (E), and duration (F) across days post-implantation. Mean ± SEM across mice. * next to line plot indicates a significant effect of day (LME model).

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques:

Journal: bioRxiv

Article Title: Chronic alteration of Ca 2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

doi: 10.1101/2025.10.23.679242

Figure Lengend Snippet: ( A ) Example epileptiform Ca 2+ activity induced by 25-Hz ICMS, showing extremely strong activation spreading across the entire visual cortex and persisting >10 s after stimulation offset (i-v, maps; vi, time courses at each distance). ( B ) Overview of Ca 2+ activity induced by 25-Hz ICMS (i), 250-Hz ICMS (ii), and visual stimulation (iii). Each line represents one mouse. ( C ) Distributions of magnitude, duration, and spatial spread of Ca 2+ activation. Colors indicate clusters identified using agglomerative clustering (see Methods). Epileptiform activity was defined from the green cluster with magnitude >100%, duration >20 s, and distance >800 µm. ( D ) Number of mice exhibiting epileptiform activity at least once across all days, conditions, and repeats (Epi) versus not (Norm). ( E ) Probability of epileptiform activity across stimulation conditions for all days, mice, and repeats. ( F ) Probability of epileptiform activity over days for all ICMS and visual stimulation conditions. Mean ± SEM across animals.

Article Snippet: Custom stimulation microelectrodes (Q1×4-3mm-50-703-CM16LP, NeuroNexus Technologies, single 3-mm-long shank, 30-μm-diameter four channels, 50-μm site spacing, electrochemically activated iridium/iridium oxide sites ) were implanted at an angle of 20-30 degrees slanted towards the posterior region.

Techniques: Activity Assay, Activation Assay