Fig. 6: Mice lacking Grik1 expression in PV interneurons are resistant to stress-induced alterations in amygdala excitability and behavior.

A Body weight changes during chronic restraint stress (CRS) protocol (Grik1^fl/fl: control n = 17, CRS n = 19; RM ANOVA, F _{(1, 34)} = 21.32, ****p < 0.0001; PV-Cre::Grik1^fl/fl: control n = 19, CRS n = 17; RM ANOVA; F _{(1, 34)} = 23.89, ****p < 0.0001). B Action potential frequencies in response to depolarizing current steps recorded from brain slices of control and CRS-treated, Grik1^fl/fl or PV-Cre::Grik1^fl/fl mice (Grik1^fl/fl: control, n = 25 (7 mice), CRS, n = 17 (6 mice), RM ANOVA, F _{(1, 40)} = 4.775, *p = 0.035; PV-Cre::Grik1^fl/fl: control, n = 19 (6 mice), CRS, n = 14 (4 mice), RM ANOVA, F _{(1, 31)} = 0.0001180, p = 0.99). C Tonic GABA_B currents recorded from LA PNs in slices from control and CRS-treated, Grik1^fl/fl or PV-Cre::Grik1^fl/fl mice. All recordings were done at −50 mV holding potential in the presence of 50 μM of D-AP5, 200 μM picrotoxin, and 50 μM GYKI 53655 to block NMDA, GABA_A, and AMPA receptors, respectively. The amplitude of the tonic current was measured as a change in the holding current in response to the application of 10 μM CGP55845. The graph illustrates averaged data on the amplitude of the tonic GABA_B currents under various conditions (Grik1^fl/fl: control, n = 15 (5 mice), CRS, n = 11 (3 mice); PV-Cre::Grik1^fl/fl: control, n = 15 (4 mice), CRS, n = 18 (3 mice); two-way ANOVA for genotype and condition, genotype effect F_(1,54) = 19.93_, ****p < 0.0001; post-hoc comparison *** p = 0.0003, Bonferroni). D Current clamp recordings from PV interneurons in acute slices from control and CRS-exposed PV-Cre::Grik1^fl/fl mice. Example traces illustrate the response of the PV neurons to depolarizing current steps (75 and 200 pA), for control and CRS groups. Pooled data on the action potential frequencies in response to depolarizing current steps (control, n = 12 (3 mice), CRS, n = 12 (3 mice), Mixed-effects model (REML) F_{(1, 22)} = 1.157, p = 0.2938). E Results of open field (OF) test. The graphs show the total time spent in the center area of the open field (OF) and the center time in 5 min bins, for control and CRS-exposed mice for the two genotypes, Grik1^fl/fl and PV-Cre::Grik1^fl/fl (Grik1^fl/fl: control, n = 16, CRS, n = 19; PV-Cre::Grik1^fl/fl: control, n = 19, CRS, n = 17). Total time in the center field: Two-way ANOVA: treatment F_{(1, 67)} = 3.086, p = 0.0835, genotype F_{(1, 67)} = 0.7517, p = 0.389, interaction F_{(1, 67)} = 4.133, p = 0.046. * p = 0.019, Holm-Sidak. Time in center zone in 5 min bins: RM ANOVA, Grik1^fl/fl: F_{(1, 34)} = 8.564, **p = 0.0062; PV-Cre::Grik1^fl/fl : F _{(1, 34)} = 0.03320, p = 0.8566. Total distance traveled: 2-way ANOVA, genotype F_(1,67) = 31.74, ****p < 0.0001, treatment F_{(1, 67)} = 1.828, p = 0.1780, interaction F_{(1, 67)} = 1.495, p = 0.2442. All the data are presented as mean ± SEM.