Figure 5: Exogenous VGAT expression in TH^CRE-positive neurons normalizes motivation and GABA co-release in TH^CRE::Ube3a^FLOX/p+ mice.

(a) Schematic representation of the experimental paradigm. DIO-VGAT and DIO-ChR2-eYFP were injected in experimental mice to selectively delete Ube3a in TH-expressing neurons and to express exogenous ChR2 and VGAT in TH⁺ VTA-to-NAc terminals. (b) Representative oIPSC evoked by single pulses (20 ms) or 30 Hz trains of stimulation. (c) Average oIPSC peak amplitudes evoked by single pulses (n=10 and 7, Student’s t-test P=0.69), and (d) average total charge evoked by 30 Hz stimulation (n=7 and 7, Student’s t-test P=0.59) demonstrate that exogenous VGAT expression in TH^CRE neurons normalizes GABA co-release between genotypes. (e) Response plots showing cumulative nose pokes that trigger a 30 Hz, 473 nm stimulus (active nose pokes) in representative mice. (f) Average nose pokes for inactive and active ports triggering 30 Hz optical intracranial self-stimulation in a 60 min behavioural session (n=6 and 6, one-way ANOVA P=0.12). Bars represent mean±s.e.m.