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Fig. 2 | Molecular Neurodegeneration

Fig. 2

From: Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors

Fig. 2

Deletion of Aldh1a1 in Aldh1a1 neurons impairs delay of gratification. a, Representative images (top) show the expression of ChR2 (left, red) in Aldh1a1 neurons and GFP in EGNIS (right, green), respectively. The illustration (bottom) shows whole-cell patch-clamp recordings from GFP-expressing EGNIS (R) and laser stimulation of ChR2-expressing Aldh1a1 synaptic terminals (S). b, Three representative IPSCs were blocked by bicuculline but not CNQX. The plot shows the rise and decay time constants (T.C) of the individual IPSCs (blue circles) and the averages (green triangles, mean ± SEM, n = 7 recordings/5 mice). c, The generation of Aldh1a1−/− mice by selective deletion of Aldh1a1 in Aldh1a1 neurons. Representative blots from two pairs of Aldh1a1+/+ and Aldh1a1−/− mice. The plot shows the normalized Aldh1a1 protein levels from the individuals (blue circles) and the averages per group (green triangles, mean ± SEM, n = 5 assays/5 mice/group). d, Aldh1a1 deletion completely blocked synaptic transmission from Aldh1a1 neurons to EGNIS. Three representative traces show the recordings of the evoked IPSCs from Aldh1a1+/+, Aldh1a1+/−, and Aldh1a1−/− mice. The plot shows the mean amplitudes of the individual IPSCs (blue circles) and the averages per group (green triangles, mean ± SEM, n = 7 recordings/3 mice/group). e, A touchscreen mouse model for delay of gratification tests, comprised of a series of the reward choice tasks, in which mice are required to choose a SIR (5 μl of chocolate milkshake at a 0-3 s delay) or a LDR (20 μl chocolate milkshake at a 6-9 s delay) versus a LLR (30 μl of chocolate milkshake at a 12-15 s delay). f, Deletion of Aldh1a1 decreases the behavioral preference for LDR. Plots show the percentage of the correct trials with the behavioral preference for SIR, LDR, or LLR of Aldh1a1+/+ (blue) and Aldh1a1−/− (green) mice at each day of the probe trials (mean ± SEM, n = 9 mice/group). g, A T-maze mouse model for delay of gratification tests, consisting of the SRA at a delay of 0-3 s and LRA at a delay of 0-3 s or 6-9 s. h, Deletion of Aldh1a1 reduces the percentage of LRA visits after a delay of 6-9 s. The plot shows the percentage of LRA visits at a delay of 0-3 s or 6-9 s from individual (circles) Aldh1a1+/+ (blue) or Aldh1a1−/− (green) mice and their averages per group (triangles, mean ± SEM, n = 11 mice/group) at day one, three and five of the testing sessions. All statistical data are summarized in Supplementary Table 1

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