The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input
Fig 7
An increase in dmPFC NE level opens a short window for transition to behavior during memory retrieval.
(A) (Left, top) Representative dmPFC NE responses to 10 s CS+ in the absence of Dulo. (Left bottom) Diagram for testing the impact of CS− on freezing levels when they were given at different time points after termination of 10 s CS+. Blue regions mark the period when CS− was given. (Right) Freezing levels during the corresponding time periods. Two-tailed paired t test, A vs. C, P < 0.001; B vs. C, P < 0.001; C vs. C/ CS−, P < 0.01. The same set of mice was used, N = 10 mice. (B) (Left) dmPFC NE signals elicited by 10 s CS+ and 30 s CS− in the absence or presence of NE uptake inhibitor Dulo. Insert: AUC of ΔF/F of dmPFC NE signals. Two-tailed unpaired t test, Dulo vs. No Dulo, P < 0.01. (Middle) Freezing levels without Dulo injection. Two-tailed paired t test, A vs. E, P < 0.001; A vs. E/CS−, P < 0.001; D vs. E, P < 0.001; D vs. E/CS−, P < 0.001. (Right) Freezing levels with Dulo injection. Two-tailed paired t test, A vs. E, P < 0.001; D vs. E, P < 0.001; E vs. E/CS−, P < 0.001. Scale bars, 0.5% ΔF/F and 10 s. The same set of mice was used, N = 10 mice. (C) Experimental protocol and stimulus patterns used (left) and corresponding freezing levels (right). One-way RM ANOVA, F (2, 8) = 0.163, Bonferroni’s posttest; CS− vs. CS+/CS−, P < 0.01; CS− vs. CS+, P < 0.001; N = 10 mice. (D) Spike rates in the T-neurons during CS retrieval (left) and AUC (z-score, 2 s) (right). One-way RM ANOVA, F (2, 72) = 4.699, Bonferroni’s posttest; CS− vs. CS+/CS−, P < 0.01; CS− vs. CS+, P < 0.05; n = 25 units/10 mice. (E) Spike rates in the S-neurons during CS retrieval (left) and AUC (z-score, 30 s) (right). One-way RM ANOVA, F (2, 33) = 2.092, Bonferroni’s posttest; CS− vs. CS+/CS−, P < 0.01; CS− vs. CS+, P < 0.01; n = 12 units/10 mice. (F) Experimental protocol for CS retrieval test, by CS+, CS−, by a hybrid stimulus (L/CS−) with opto-activation of LA axonal terminals in dmPFC for 2 s followed immediately by CS− (left) and corresponding freezing levels during retrieval (right). One-way RM ANOVA, F (2, 18) = 3.807, Bonferroni’s posttest; CS− vs. L/CS−, P < 0.05; N = 6 mice. (G) Spike rates in the T-neurons (left) and AUC (z-score, 2 s) (right). One-way RM ANOVA, F (2, 42) = 6.67, Bonferroni’s posttest; CS− vs. L/CS−, P < 0.001; CS− vs. CS+, P < 0.05; n = 13 units/6 mice. (H) Spike rates in the T-neurons (left) and AUC (z-score, 30 sec) (right). One-way RM ANOVA, F (2, 18) = 5.099, Bonferroni’s posttest; CS− vs. L/CS−, P < 0.001; CS− vs. CS+, P < 0.001; n = 16 units/6 mice. Numerical data can be found in S1 Data.