Journal: bioRxiv
Article Title: Midbrain Tet1 dosage defines inter-individual binge-eating susceptibility
doi: 10.64898/2026.03.14.711800
Figure Lengend Snippet: (A) Schematic of retrograde labeling of input projection neurons to the VTA using AAV.rg-hSyn1-EGFP. (B) Micrograph of an exemplary coronal brain section upon machine learning-assisted brain region mapping (Aligning Big Brains & Atlases (ABBA/ImageJ)). Back-labeled neurons are highlighted in the mPFC and LHA. (C) Circos plot showing relative input strength from reward-related regions to the VTA comparing eBED-prone versus-resilient Tet1 +/– mice (upper panel); corresponding binge sizes of individual Tet1 +/- mice across 5 eBED days plotted on a Log 10 scale to visualize varied responses (lower panel; shaded area shows normal binge response). Data are presented as mean minimum to maximum values. ** P < 0.01. n = 4 mice (unpaired Student’s t -test). (D) Coronal brain schematics of mPFC subregions ( PL : prelimbic; Cg1 : dorsal cingulate cortex; Cg2 : ventral cingulate cortex). (E) Representative micrographs of mPFC PL from eBED-prone versus-resilient Tet1 +/− mice. Scale bar 100 μm. (F) Bar graphs of raw EGFP density values from mPFC subregions hemisections ( PL : prelimbic; Cg1 : dorsal cingulate cortex; Cg2 : ventral cingulate cortex). Data are presented as mean ± SEM. * P < 0.05. n = 4 mice (two-tailed unpaired Student’s t -test). (G) Schematic illustrating chemogenetic approach to selectively inhibit VTA-projecting mPFC PL neurons using a dual AAV approach (AAV.rg-Cre + AAV-hSyn1-FLEX-hM4Di-mCherry). (H) Micrograph of VTA-projecting mPFC PL neurons expressing mCherry (red) intermingled with layer-5 pyramidal neurons (CTIP2: grey). Scale bar: 500 μm and 50 μm (insert). (I) Cumulative binge intake of hM4Di mPFC-VTA mice and controls per individual days (left panel). Data are presented as mean ± SEM. *** P < 0.001, **** P < 0.0001. n = 4–5 mice (multiple unpaired Student’s t -test); mean binge sizes of hM4Di mPFC-VTA mice and controls (right panel). Data are presented as mean and minimum to maximum. * P < 0.05, n = 4–5 mice (one-tailed unpaired Student’s t -test).
Article Snippet: To perform brain-wide mapping of VTA inputs, AAV rg -hSyn1-EGFP (Addgene, #105553, 7E12 GC/mL) was bilaterally injected into the VTA of 6–8-week-old Tet1 +/– mice and littermate controls.
Techniques: Labeling, Two Tailed Test, Expressing, One-tailed Test
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