Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context - PubMed (original) (raw)

Fig. 2.

Optogenetic inhibition of LC axonal terminals in CA3 impairs contextual memory formation at the encoding stage. (A) Double-transgenic mice were generated by crossing NET-Cre mice with Cre-dependent Arch-EGFP mice. (B_–_D) Images of sagittal sections show LC-specific expression of Arch-EGFP fusion protein (green) and immunoreactivity with anti-NET antibody (red). (E) Behavioral schedule used for the novel-context recognition test to test memory encoding. The green trapezoid represents the timing of light delivery. The photoinhibition was given for the entire sampling sessions. (F_–_I, Upper) The placement of optic fibers targeting the LC cell body (day × genotype, _F_1,22 = 4.749, P < 0.05; n = 13 for control and n = 11 for the Arch group) (F), DG (day × genotype, _F_1,10 = 0.5853, P = 0.4619; day, _F_1,10 = 78.27, P < 0.0001; genotype, _F_1,10 = 4.112, P = 0.0701; n = 6 per group) (G), CA3 (day × genotype, _F_1,12 = 6.543, P < 0.05; n = 7 per group) (H), and CA1 (day × genotype, _F_1,10 = 0.1798, P = 0.6805; day, _F_1,10 = 33.25, P < 0.0005; genotype, _F_1,10 = 2.144, P = 0.1739; n = 6 per group) (I). (Lower) Travel distances were tracked and averaged over 4-min sessions. (J) Behavioral schedule to test memory recall. (K and L, Upper) The placement of optic fibers targeting the LC cell body (day × genotype, _F_1,10 = 0.1032, P = 0.7547; day, _F_1,10 = 21.14, P < 0.001; genotype, _F_1,10 = 0.0007817, P = 0.9782; n = 6 per group) (K) and CA3 (day × genotype, _F_1,12 = 0.2397, P = 0.6332; day, _F_1,12 = 45.59, P < 0.0001; genotype, _F_1,12 = 1.115, P = 0.3118; n = 6 per group) (L). (Lower) Travel distances were tracked and averaged over 4-min sessions. (M) Behavioral schedule for preexposure-dependent CFC. Green bars represent the timing of light delivery. (N and O) Freezing levels were averaged over 5-min test sessions in the conditioned context B (test 1) and unconditioned context C (test 2). Photoinhibition was delivered at context preexposure (PE) sessions (n =7 per group) (N) or at IS sessions (n = 8 per group) (O). Statistical comparisons were performed using two-way repeated-measures ANOVA and post hoc Sidak’s multiple comparisons test (F_–_I, K, and L) and unpaired t tests (N and O); ****P < 0.001 **P < 0.01; *P < 0.05; n.s., not significant. Data are presented as mean ± SEM.