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The effects of chronic CM DRN modulation on htau behaviors. A, Graphical overview of the htau DREADDs experiment. Htau mice were intracranially administered hM3Dq ( n = 14), hM4Di ( n = 14), or control virus ( n = 9) at 2 months’ age. DREADDs agonist <t>(CNO</t> <t>DHC)</t> was administered via water bottle for 6 weeks. B, C, RNAscope assessment of Fos expression in virally transduced Tph2 + cells before CNO washout (acute) and after 7‐day washout. Two data points were collected per mouse in (C). No statistical test was performed in (C), data were qualitatively compared. D, E, NOR. D, Percent preference for novel object and (E), discrimination index. 1w ANOVA with Tukey post hoc. F, G, NSF. F, Latency to feed and (G), time spent in the corners of the arena during 10‐minute assessment period. H–K, EPM task. H, Percent of total time spent in open arm, (I) entries to open arm, (J) total distance traveled, and (K) average velocity during the task. L–R, Three‐chamber SIT. L, Total social interaction time, (M) number of social interactions, (N) social interaction time as a percentage of time spent in the social chamber, and (O) time spent in the center chamber. P–R, Representative heat maps, normalized within trial. D–F, H–K, 1w ANOVA with Dunnett post hoc. G, 1w Welch ANOVA with Dunnett post hoc. L–O, 1w ANOVA with Tukey post hoc. * p < 0.05, ** p < 0.01. 1w, one way; ANOVA, analysis of variance; CM, centromedial; CNO, clozapine‐n‐oxide; DHC, dihydrochloride; DREADDs, designer receptors exclusively activated by designer drugs; DRN, dorsal raphe nucleus; EPM, elevated plus maze; NOR, novel objection recognition; NSF, novelty‐induced suppression of feeding; SIT, social interaction test.
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The effects of chronic CM DRN modulation on htau behaviors. A, Graphical overview of the htau DREADDs experiment. Htau mice were intracranially administered hM3Dq ( n = 14), hM4Di ( n = 14), or control virus ( n = 9) at 2 months’ age. DREADDs agonist <t>(CNO</t> <t>DHC)</t> was administered via water bottle for 6 weeks. B, C, RNAscope assessment of Fos expression in virally transduced Tph2 + cells before CNO washout (acute) and after 7‐day washout. Two data points were collected per mouse in (C). No statistical test was performed in (C), data were qualitatively compared. D, E, NOR. D, Percent preference for novel object and (E), discrimination index. 1w ANOVA with Tukey post hoc. F, G, NSF. F, Latency to feed and (G), time spent in the corners of the arena during 10‐minute assessment period. H–K, EPM task. H, Percent of total time spent in open arm, (I) entries to open arm, (J) total distance traveled, and (K) average velocity during the task. L–R, Three‐chamber SIT. L, Total social interaction time, (M) number of social interactions, (N) social interaction time as a percentage of time spent in the social chamber, and (O) time spent in the center chamber. P–R, Representative heat maps, normalized within trial. D–F, H–K, 1w ANOVA with Dunnett post hoc. G, 1w Welch ANOVA with Dunnett post hoc. L–O, 1w ANOVA with Tukey post hoc. * p < 0.05, ** p < 0.01. 1w, one way; ANOVA, analysis of variance; CM, centromedial; CNO, clozapine‐n‐oxide; DHC, dihydrochloride; DREADDs, designer receptors exclusively activated by designer drugs; DRN, dorsal raphe nucleus; EPM, elevated plus maze; NOR, novel objection recognition; NSF, novelty‐induced suppression of feeding; SIT, social interaction test.
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The effects of chronic CM DRN modulation on htau behaviors. A, Graphical overview of the htau DREADDs experiment. Htau mice were intracranially administered hM3Dq ( n = 14), hM4Di ( n = 14), or control virus ( n = 9) at 2 months’ age. DREADDs agonist (CNO DHC) was administered via water bottle for 6 weeks. B, C, RNAscope assessment of Fos expression in virally transduced Tph2 + cells before CNO washout (acute) and after 7‐day washout. Two data points were collected per mouse in (C). No statistical test was performed in (C), data were qualitatively compared. D, E, NOR. D, Percent preference for novel object and (E), discrimination index. 1w ANOVA with Tukey post hoc. F, G, NSF. F, Latency to feed and (G), time spent in the corners of the arena during 10‐minute assessment period. H–K, EPM task. H, Percent of total time spent in open arm, (I) entries to open arm, (J) total distance traveled, and (K) average velocity during the task. L–R, Three‐chamber SIT. L, Total social interaction time, (M) number of social interactions, (N) social interaction time as a percentage of time spent in the social chamber, and (O) time spent in the center chamber. P–R, Representative heat maps, normalized within trial. D–F, H–K, 1w ANOVA with Dunnett post hoc. G, 1w Welch ANOVA with Dunnett post hoc. L–O, 1w ANOVA with Tukey post hoc. * p < 0.05, ** p < 0.01. 1w, one way; ANOVA, analysis of variance; CM, centromedial; CNO, clozapine‐n‐oxide; DHC, dihydrochloride; DREADDs, designer receptors exclusively activated by designer drugs; DRN, dorsal raphe nucleus; EPM, elevated plus maze; NOR, novel objection recognition; NSF, novelty‐induced suppression of feeding; SIT, social interaction test.

Journal: Alzheimer's & Dementia

Article Title: Selective reduction of KCNA4 in vulnerable glutamatergic–serotonin neurons of the dorsal raphe nucleus in Alzheimer's disease

doi: 10.1002/alz.71317

Figure Lengend Snippet: The effects of chronic CM DRN modulation on htau behaviors. A, Graphical overview of the htau DREADDs experiment. Htau mice were intracranially administered hM3Dq ( n = 14), hM4Di ( n = 14), or control virus ( n = 9) at 2 months’ age. DREADDs agonist (CNO DHC) was administered via water bottle for 6 weeks. B, C, RNAscope assessment of Fos expression in virally transduced Tph2 + cells before CNO washout (acute) and after 7‐day washout. Two data points were collected per mouse in (C). No statistical test was performed in (C), data were qualitatively compared. D, E, NOR. D, Percent preference for novel object and (E), discrimination index. 1w ANOVA with Tukey post hoc. F, G, NSF. F, Latency to feed and (G), time spent in the corners of the arena during 10‐minute assessment period. H–K, EPM task. H, Percent of total time spent in open arm, (I) entries to open arm, (J) total distance traveled, and (K) average velocity during the task. L–R, Three‐chamber SIT. L, Total social interaction time, (M) number of social interactions, (N) social interaction time as a percentage of time spent in the social chamber, and (O) time spent in the center chamber. P–R, Representative heat maps, normalized within trial. D–F, H–K, 1w ANOVA with Dunnett post hoc. G, 1w Welch ANOVA with Dunnett post hoc. L–O, 1w ANOVA with Tukey post hoc. * p < 0.05, ** p < 0.01. 1w, one way; ANOVA, analysis of variance; CM, centromedial; CNO, clozapine‐n‐oxide; DHC, dihydrochloride; DREADDs, designer receptors exclusively activated by designer drugs; DRN, dorsal raphe nucleus; EPM, elevated plus maze; NOR, novel objection recognition; NSF, novelty‐induced suppression of feeding; SIT, social interaction test.

Article Snippet: After a 7‐day recovery period, mice were continuously administered the DREADD agonist CNO DHC (clozapine‐n‐oxide dihydrochloride; cat. #HB6149; Hello Bio) at a concentration of 6.06 mg/mL (equivalent to 5 mg/mL CNO) via water bottle in a home‐cage environment.

Techniques: Control, Virus, RNAscope, Expressing