Fig. 5: Highly active VIP neurons are most susceptible to the effects of stroke and chemogenetic therapy. | Nature Communications

Fig. 5: Highly active VIP neurons are most susceptible to the effects of stroke and chemogenetic therapy.

From: Longitudinal functional imaging of VIP interneurons reveals sup-population specific effects of stroke that are rescued with chemogenetic therapy

Fig. 5

a VIP neurons were classified as highly, moderately or minimally active neurons based on the fidelity of their responses before stroke (highly, moderately and minimally active cell responds to 6–8, 3–5, and 0–2 trials respectively). Graphs show the effect of stroke (n = 6 and 7 mice for Stroke control and Stroke hM3Dq, respectively) or sham (n = 4 mice) procedure on the % forelimb responsive trials in each neuron subpopulation. Chemogenetic stimulation protects against the loss of response fidelity in highly active neurons (two-way ANOVA, Main effect of hM3Dq: F(1,33) = 19.75, p < 0.0001), and to a lesser extent in moderately active neurons (two-way ANOVA, Main effect of hM3Dq: F(1,33) = 8.24, p = 0.007), while there was no effect in minimally active neurons (two-way ANOVA, Main effect of hM3Dq: F(1,33) = 1.72, p = 0.20). b To understand how response profiles can change over time, each neuron was assigned to one of the 3 categories and then followed over time after sham stroke (highly, moderately, minimally active = 42, 29, 45 neurons, respectively) or stroke with or without chemogenetic stimulation (Stroke hM3Dq = 44, 69, 84 neurons and Stroke control = 36, 70, 48 neurons). Far right: graphs show the proportion of each neuron class (out of 100%) averaged over weeks 1–3 relative to pre-stroke. c Montage showing forelimb-evoked calcium responses in a neuron (white arrow) that was minimally responsive before stroke, but became highly responsive afterwards. d Graphs comparing proportion (out of 100%) of high, moderate or minimally active neurons before stroke versus 1–3 weeks afterwards. Chi-squared (χ2) analysis revealed no significant changes in Sham stroke or Stroke hM3Dq groups (all χ2 values range from 0.01 to 0.38; all p values > 0.05). Stroke control stimulation mice exhibited significantly fewer highly active neurons (χ2 = 4.91, p < 0.05) and more minimally active neurons after stroke (χ2 = 13.73, p < 0.01). +p < 0.05, ++p < 0.01 for two-sided χ2 comparison. #p < 0.05, ##p < 0.01, ###p < 0.001 for t-test comparisons against pre-stroke. *p < 0.05, **p < 0.01, ***p < 0.001 for t-test comparisons between Stroke hM3Dq vs Stroke Control. n.s. not significant. Data show means ± S.E.M.

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