Extended Data Fig. 9: Optogenetic activation of lOFC inhibitory neurons restores devaluation in obesity.
From: Disinhibition of the orbitofrontal cortex biases decision-making in obesity
a) Electrophysiology validation of ChR2 expressed in GABAergic neurons of the lOFC. Example traces of current evoked (pA) from a lOFC GABAChR2 neuron to a train of light pulses delivered at 5 Hz for 4 ms (5 mW). b) Electrophysiology validation of ChR2 expressed in GABAergic neurons of the lOFC. Example traces of current evoked (pA) from a lOFC GABAChR2 neuron to a single 500 ms pulse in voltage clamp. This was reliably repeated in several different brain slices from VGATcre mice. c) VGATcre mice exposed to the high-fat diet (n = 7) weighed more than lean mice (n = 8) prior to behavioral testing for devaluation by selective satiety. Unpaired t-test: t (13) =7.531, p < 0.0001****. Data are presented as mean values + /− SEM. d) Lean (n = 8) and obese (n = 7) VGATcre mice were trained to lever press (RR5, RR10, and RR20 training) for sucrose prior to behavioral testing on the devaluation task. Two-way ANOVA mixed effects model: training schedule effect: F (1.504, 19.55) = 9.122, p = 0.0031**, Diet effect: F (1, 13) = 32.23, P < 0.0001****, Schedule of reinforcement and diet interaction: F (2, 26) = 4.331, p = 0.0238 *. Dunnett’s multiple comparisons: Lean RR5 vs RR10 p = 0.9403, lean RR5 vs RR20 p = 0.0662, obese RR5 vs RR20 p = 0.0109*, obese RR5 vs RR20 p = 0.0108*. Data are presented as mean values + /− SEM. e) Lean (lean inactive 589 nm n = 8, lean active 473 nm n = 8) and obese (obese inactive 589 nm n = 6, obese active 473 nm n = 7) mice consumed similar amounts of sucrose prior to the selective satiety procedure. Two-way ANOVA mixed effects model: Diet effect F (1, 13) = 0.02776, p = 0.8702, Stimulation effect F (1, 11) = 1.468, p = 0.2510, diet × stimulation interaction F (1, 11) = 1.468, 0.2510. Data are presented as mean values + /− SEM. f) Total distance traveled (m) of lean (n = 6) and obese (n = 3) mice in a one-hour open field test immediately following photo-stimulation (589 nm inactive or 473 nm active) of lOFC GABAergic neurons. Two-way RM ANOVA: Interaction: F (1, 7) = 0.01176, p = 0.9167, Diet effect: F (1, 7) = 3.399, p = 0.1078 photostimulation effect: F (1, 7) = 0.8146, p = 0.3967. Data are presented as mean values + /− SEM.
