Fig. 3: Inhibition of PL-NAc core pathway leads to compulsivity. | Nature Communications

Fig. 3: Inhibition of PL-NAc core pathway leads to compulsivity.

From: A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction

Fig. 3

a Scheme of combinatorial viral strategy for selective hM4Di-mCherry expression in PL-NAc core neurons. b Representative immunofluorescence images of Cre-dependent hM4Di-mCherry detected at PL injection site (left) and Cre recombinase at NAc core (right). c–f Chemogenetic inhibition of glutamatergic PL-NAc core neurons induces changes in excitatory transmission in the PL and NAc core. c Representative recordings showing evoked (200 pA) action potential in WT mice injected with AAV-control (left) and AAV-hM4Di (right) in PL layer 5 mCherry visualized neurons at baseline and after CNO (10 µM) application. d Quantification of the firing rate (Hz) (mean and individual values; paired t-test, *P < 0.05; n = 14 cells from n = 4 mice injected with AAV-control and n = 10 cells from n = 4 animals injected with AAV-hM4Di). e Representative traces of miniature excitatory postsynaptic currents (mEPSCs) recorded at a holding potential of −75 mV in NAc from mice injected with AAV-control (left) or AAV-hM4Di (right) in baseline and after CNO (10 µM) bath application (above). Cumulative probability plot of the mEPSCs amplitude from both control (left) and hM4Di (right) expressing mice in baseline conditions and after CNO (10 µM) bath application (below). f Changes of mEPSCs frequency in percentage (mean and individual values; paired t-test, *P < 0.05; n = 8  cells from n = 6 mice injected with AAV-control and n = 8 cells from n = 7 mice injected with AAV-hM4Di). g Timeline of the experimental sequence of the early period of food addiction mouse model. h Number of reinforcers during operant training sessions maintained by chocolate-flavored pellets (mean ± S.E.M). i–k Behavioral tests of the three addiction-like criteria showing increased compulsivity in CNO-treated mice (individual values with the median and the interquartile range, U Mann–Whitney, **P < 0.01). The 75th percentile of distribution of mice treated with saline is indicated by the dashed horizontal line. Addicted mice in gray filled circles for saline-treated mice and red for CNO-treated mice. l Increased percentage of CNO-treated mice classified as food addicted animals (chi-square, ***P < 0.001). m–o Pearson correlations between individual addiction-like criteria and m non-reinforced active responses in 10 min, n breaking point in 5 h, o number of shocks in 50 min (n = 12 for saline-treated mice and n = 22 for CNO-treated mice; PL prelimbic, NAc nucleus accumbens, Amg amygdala, Hip hippocampus, VTA ventral tegmental area, ACC anterior cingulate cortex, IL infralimbic; see also Supplementary Fig. 6; statistical details are included in Supplementary Table 4).

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