Fig. 4: Balance between acetylcholine- and dopamine-release in anxiety and social motivation conditions.
From: Altered acetylcholine modulations and corticoaccumbal pathway in P11-linked social dysfunction
(A, B) Injection of dopamine- (AAV-rGRAB-DA, red) and acetylcholine-sensor (AAV-Ach-SnFr, green) virus in VTA of P11-WT or P11-KO mice allows recording of dopamine and acetylcholine release in medial VTA using fiber photometry. (C-G) Variation of the GFP-isosbestic control channel (left, P > 0.05), acetylcholine (middle), and dopamine release (right panel) in 5 s windows surrounding entry to the light area in a light OFF condition (C, Ach-sensor: paired t-tests baseline versus entries, P11-WT P = 0.1547, P11-KO P = 0.05112, DA-sensor: paired t-tests P11-WT P = 0.365, P11-KO P = 0.544), light ON (D Ach-sensor: paired t-tests P11-WT P = 0.041, P11-KO P = 2.10^-9, genotype unpaired t-test P = 0.0061; DA-sensor: paired t-tests P11-WT P = 0.0004, P11-KO P = 8.10^-6, genotype unpaired t-test P = 0.5227) and with a conspecific of the same sex animal in the light area (E Ach-sensor: paired t-tests P11-WT P = 0.6142, P11-KO P = 4.10^-6, genotype unpaired t-test P = 0.004; DA-sensor: paired t-tests P11-WT P = 8.10^-5, P11-KO P = 3.10^-5, genotype unpaired t-test P = 0.0416) in P11-WT (black) and P11-KO (red) mice. Variation of the GFP-isosbestic control channel (left), acetylcholine (middle, paired t-test P11-WT interacting with P11-WT: P = 0.0224; P11-WT interacting with P11-KO: P = 0.0776; P11-KO interacting with P11-WT P = 0.6402, P11-KO interacting with P11-KO P = 0.2471), and dopamine release (right panel, paired t-test P11-WT interacting with P11-WT: P = 0.8482; P11-WT interacting with P11-KO: P = 0.7933; P11-KO interacting with P11-WT P = 0.0027, P11-KO interacting with P11-KO P = 0.0144) in a 5 s window surrounding sniffing of P11-WT (F) and P11-KO (G). (H, I) Injection of dopamine- (Aav-RgRAB-DA) and acetylcholine-sensor (AAV-Ach-SnFr) virus in the Nac (H) of P11-WT or P11-KO mice allow recording of dopamine and acetylcholine release in Nac using fiber photometry (I). (J-N) Variation of the GFP-isosbestic control channel (left), acetylcholine (middle), and dopamine release (right panel) in a 5 s window surrounding entry to the light area in a light OFF condition (J), light ON (K Ach-sensor: paired t-tests P11-WT P = 0.105, P11-KO P = 291, genotype unpaired t-test P = 0.1792; DA-sensor: paired t-tests P11-WT P = 0.004, P11-KO P = 0.028, genotype unpaired t-test P = 0.0003) and with a conspecific of the same sex animal in the light area (L, Ach-sensor: paired t-tests P11-WT P = 0.468, P11-KO P = 0.041, genotype unpaired t-test P = 0.0119; DA-sensor: paired t-tests P11-WT P = 0.043, P11-KO P = 0.262, genotype unpaired t-test P = 0.1299) in P11-WT (black) and P11-KO (red) mice. Variation of the GFP-isosbestic control channel (left), acetylcholine (middle, paired t-test P11-WT interacting with P11-WT: P = 0.1561; P11-WT interacting with P11-KO: P = 0.4121; P11-KO interacting with P11-WT P = 0.93, P11-KO interacting with P11-KO P = 0.011) and dopamine release (right panel, paired t-test P11-WT interacting with P11-WT: P = 0.0407; P11-WT interacting with P11-KO: P = 7.10^-8; P11-KO interacting with P11-WT P = 0.8592, P11-KO interacting with P11-KO P = 0.43) in a 5 s window surrounding sniffing of P11-WT (M) and P11-KO (N). (O) Schematic representation of the variation of dopamine (red) and acetylcholine (green) release during the dark-light area, dark-light social, and sniffing. Data are represented as z-score normalization of the ΔF/F0. Statistical analyses are between the baseline versus entry time (top) or between the P11-WT and P11-KO (right side). *P < 0.05.
