Journal: iScience
Article Title: Response dynamics of discrete subiculum→retrosplenial cortex projections underlying trace fear conditioning
doi: 10.1016/j.isci.2026.115317
Figure Lengend Snippet: VGluT2 + SUB→RSP afferents are specifically required for processing a temporal trace separating a cue and a shock (A, D, and G) Experimental design of behavioral tasks. Diagrams depict virus infusion sites in DH and cannula placements for CNO injections in RSP (top and right), and viral expression in RSP and DH (bottom and right). (B) When compared to vehicle, CNO injections 30 min before TFC training, impaired freezing at test in response to both the tone and trace periods in mice receiving AAV-hM4D (Gi) ( n = 9–10; two-way ANOVA with repeated measures; factor: treatment, p = 0.0098, F (1, 17) = 8.444, factor: phase, p < 0.0001, F (2, 34) = 67.41, factor: trial × phase, p = 0.0084, F (2, 34) = 5.522). (C) CNO injection before training in delay fear conditioning (DFC) did not affect freezing to tone or post-tone when compared to vehicle-injected mice ( n = 9–10; two-way ANOVA with repeated measures; factor: treatment, p = 0.6738, F (1, 17) = 0.1835, factor: phase, p < 0.0001, F (2, 34) = 97.84, factor: trial × phase, p = 0.1764, F (2, 34) = 1.827). (E) In VGluT2-Cre mice, CNO injection 30 min before training significantly impaired freezing during the trace but not tone compared to vehicle group ( n = 10; two-way ANOVA with repeated measures; factor: treatment, p = 0.0132, F (1, 18) = 7.565, factor: phase, p < 0.0001, F (2, 36) = 41.47, factor: trial × phase, p = 0.0001, F (2, 36) = 12.00. (F) In VGluT1-Cre mice, terminal silencing with CNO did not affect freezing compared to vehicle controls ( n = 9; two-way ANOVA with repeated measures; factor: treatment, p = 0.0931, F (1, 16) = 3.189, factor: phase, p < 0.0001, F (2, 32) = 13.78, factor: trial × phase, p = 0.9968, F (2, 32) = 0.003253) when compared to vehicle controls. (H) Injections of CNO ( n = 10) before trace-light conditioning (TLC) training did not affect freezing during either the tone or light periods in mice expressing inhibitory DREADD only in VGluT2 + SUB→RSP projections ( n = 10; two-way ANOVA with repeated measures; factor: treatment, p = 0.2577, F (1, 18) = 1.366, factor: phase, p < 0.0001, F (2, 36) = 52.27, factor: trial × phase, p = 0.5714, F (2, 36) = 0.5685). (I) Injections of CNO before TLC training significantly impaired freezing to both tone and light when compared to vehicle in mice expressing inhibitory DREADD in all SUB→RSP projections compared to vehicle injected group ( n = 5–6; two-way ANOVA with repeated measures; factor: treatment, p = 0.0087, F (1, 9) = 11.12, factor: phase, p < 0.0001, F (2, 18) = 19.01, factor: trial × phase, p = 0.3846, F (2, 18) = 1.008. Data presented as mean ± SEM ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001; NS, not significant; WT, wild-type. All scale bars, 250 μm.
Article Snippet: Wild type C57BL6/J mice were purchased from Harlan, Indianapolis, IN.
Techniques: Virus, Expressing, Injection
