Fig. 3
From: Midbrain circuit regulation of individual alcohol drinking behaviors in mice
Phasically activating VTA dopamine neurons reduces high alcohol drinking behaviors. a Timeline of experiments and schematic of surgeries in TH-BAC-Cre mice. High alcohol drinking TH-BAC-Cre mice expressing either AAV5-DIO-eYFP (eYFP, control vector) or AAV5-DIO-ChR2-eYFP (ChR2) were selected following the alcohol drinking paradigm to undergo bilateral optic ferrule implantation into the VTA followed by phasic optical stimulation. b Colocalization of AAV-DIO-ChR2-eYFP in TH+ neurons of the VTA. n = 374 cells from 8 mice, scale bar = 150 μm. c Electrophysiological validation of phasic light stimulation via ChR2 in VTA dopamine (DA) neurons eliciting action potentials (left) and (middle) inward currents in vitro and burst firing in vivo. d EtOH preference of high alcohol drinking mice following 15 min phasic stimulation of VTA DA neurons (two-way RM ANOVA: interaction effect F(3,33) = 2.922, P < 0.05; drinking group effect F(1,33) = 5.765, P < 0.05; time effect F(3,33) = 4.258, P < 0.05; Bonferroni post hoc test, eYFP vs ChR2. *P < 0.05 at 24 and 48 h. n = 5 mice; n = 8 mice). e (Top) In vivo validation of 5 Hz stimulation in VTA DA neurons and (bottom) EtOH preference between eYFP and ChR2 high alcohol drinking mice 24 h following 15 min 5 Hz stimulation of VTA DA neurons (two-way RM ANOVA: interaction effect F(3,36) = 1.197, P > 0.05; drinking group effect F(1,36) = 0.06571, P > 0.05; time effect F(3,36) = 1.953, P > 0.05; Bonferroni post hoc test, P > 0.05. n = 7 mice; n = 7 mice). f (Top) In vivo validation of 0.5 Hz stimulation in VTA DA neurons and (bottom) EtOH preference between eYFP and ChR2 high alcohol drinking mice 24 h following 15 min 0.5 Hz stimulation of VTA DA neurons (two-way RM ANOVA: interaction effect F(3,48) = 0.4922, P > 0.05; drinking group effect F(1,48) = 0.02455, P > 0.05; time effect F(3,48) = 3.451, P < 0.05; Bonferroni post hoc test, P > 0.05. n = 10 mice; n = 8 mice). g (Top) Timeline and schematic, TH-BAC-Cre mice received AAV5-DIO-eYFP (eYFP, control vector) or AAV5-DIO-ChR2-eYFP (ChR2), and bilateral optic ferrule implantation into the VTA. (Bottom) EtOH preference between eYFP and ChR2 EtOH naive mice 24 h following 15 min 5 Hz stimulation of VTA DA neurons (two-way RM ANOVA: interaction effect F(2,28) = 0.7363, P > 0.05; drinking group effect F(1,28) = 0.9406, P > 0.05; time effect F(2,28) = 1.981, P > 0.05; Bonferroni post hoc test, P > 0.05. n = 7 mice; n = 9 mice). Data represented as mean + S.E.M.
