(a) Schematic illustration of optogenetic activation in the AHN (green circle depicts the AAV infusion). (b) Schematic describing the RTPA and CPA test paradigm: day 1 consisting of habituation and real-time place preference (20 min) and day 2 for testing conditioned place preference (5 min). (c) Chamber preference during habituation (GFP N=14, ChR2 N=12, unpaired t-test, t=1.390, df=24, p=0.1772, NS). (d) Distance travelled during habituation (GFP N=14, ChR2 N=12, unpaired t-test, t=0.8396, df=24, p=0.41, NS). (e) Representative locomotion trajectory for a GFP control animal (left column) and a ChR2-expressing animal (right column) during habituation (hab), 6 Hz or 20 Hz real-time stimulation (6 Hz RTPA, 20 Hz RTPA), and conditioned place aversion test (Retrieval). Light-coupled chambers are shown in blue. (f) Realtime place aversion monitored across 20-min test (GFP N=7, ChR2 N=6). GFP 6 Hz vs. ChR2 6 Hz (two-way RM ANOVA, time x treatment, F(3,33)=3.965, *p=0.016, time effect, F(2.252, 24.77)=4.739, p=0.152, NS, treatment effect, F(1, 11)=77.41, ****p<0.0001, Sidak’s multiple comparisons test, 0-5 min, *p=0.0359, 5-10 min, ****p<0.0001, 10-15 min, **p=0.0022, 15-20 min, ****p<0.0001). GFP 20 Hz vs. ChR2 20 Hz (two-way RM ANOVA, time x treatment, F(3,33)=0.6059, p=0.6158, NS, time effect, F(1.938, 21.32)=1.305, p=0.2911, NS, treatment effect, F(1,11)=43.38, ****p<0.0001, 24 multiple comparisons test, 0-5 min, ***p=0.0008, 5-10 min, ****p<0.0001, 10-15 min, ***p=0.0007, 15-20 min, *p=0.0127). GFP 6 Hz vs. GFP 20 Hz (two-way RM ANOVA, time x frequency, F(2.071, 12.42)=1.076, p=0.3730, NS, time effect, F(1.964, 11.78)=0.5391, p=0.5939, NS, frequency effect, F(1, 6)=0.2474, p=0.6366, NS, Sidak’s multiple comparisons test, 0-5 min, p=0.8256, NS, 5-10 min, p=0.8824, NS, 10-15 min, p=0.9794, NS, 15-20 min, p=0.9995, NS). ChR2 6 Hz vs. ChR2 20 Hz (2-WAY RM ANOVA, time x frequency, F(1.455, 7.274)=7.391, *p=0.0223, time effect, F(1.514, 7.571)=11.05, **p=0.0075, frequency effect, F(1, 5)=20.99, **p=0.0059, Sidak’s multiple comparisons test, 0-5 min, ***p=0.0008, 5-10 min, p=0.2586, NS, 10–15 min, p=0.5763, NS, 15–20 min, p=0.3504, NS). (g) Distance travelled during 6 Hz and 20 Hz real-time stimulation (2-WAY ANOVA, frequency x genotype, F(1,22)=2.581, p=0.1224, NS, frequency effect, F(1, 22) = 0.3967, p=0.5353, NS, genotype effect, F(1, 22)=0.5732, p=0.457, NS, Sidak’s multiple comparisons test, 6 Hz GFP vs. ChR2, p=0.8013, NS, 20 Hz GFP vs. ChR2, p=0.2058, NS). (h) Conditioned aversion memory tested 24-hr after real time place aversion tests (two-way ANOVA, frequency x genotype, F(1,22)=6.208, *p=0.0207, frequency effect, F(1, 22) = 9.411, **p=0.0056, genotype effect, F(1, 22)=31.19, ****p<0.0001, Sidak’s multiple comparisons test, 6 Hz GFP vs. ChR2, p=0.0778, NS, 20 Hz GFP vs. ChR2, ****p<0.0001). (i) Distance travelled during the conditioned place aversion test (two-way ANOVA, frequency x genotype, F(1,22)=0.2058, p=0.6545, NS, frequency effect, F(1, 22) = 1.998, p=0.1715, NS, genotype effect, F(1, 22)=0.06095, p=0.8073, NS, Sidak’s multiple comparisons test, 6 Hz GFP vs. ChR2, p=0.8596, NS, 20 Hz GFP vs. ChR2, p=0.9868, NS). All results reported are mean ± s.e.m. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Figure 2—source data 1. Numerical data shown in Figure 2.AHN stimulation is aversive and induces conditioned place aversion.