Fig. 6: Activation of BF cholinergic neurons that project to the PFC reverses cognitive deficits in ChatCRECul3F/+ mice. | Translational Psychiatry

Fig. 6: Activation of BF cholinergic neurons that project to the PFC reverses cognitive deficits in ChatCRECul3F/+ mice.

From: Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits

Fig. 6

A, B Hypoactivation of cortical neurons as measured by reduced levels of rpS6-Ser235/236 (A) and decreased number of Arc+ cells (B) in the PFC of ChatCRECul3F/+ mice, compared to Cul3F/+ littermates (n = 24 slices/6 Cul3F/+ mice, n = 22 slices/6 ChatCRECul3F/+ mice, A, t(44) = 2.16, p = 0.036, B, t(44) = 4.25, p < 0.0001, unpaired two-tailed t-test). Scale bar 40 µm. C Schematic representation of stereotaxic delivery of floxed retrograde hM3D(Gq) DREADD AAV into the PFC of ChatCRECul3F/+ mice. D Confocal images showing DREADD mCherry in the BF (left) and Cre-dependent recombination in ChAT+ neurons (right). Scale bar: left 1 mm, right 20 µm. E Improved cognitive performance in the TORM test of ChatCRECul3F/+ mice after CNO administration to activate the cholinergic BF to PFC pathway (Cul3F/+: n = 8, ChatCRECul3F/+: n = 13, Finteraction(1, 38) = 9.107, p = 0.0045; Fgenotype(1, 38) = 9.211, p = 0.0043; Ftreatment(1,38) = 4.887, p = 0.0332, two-way ANOVA). F PPI deficits in ChatCRECul3F/+ mice are unchanged by CNO administration (Startle: Finteraction(9, 111) = 1.75, p = 0.086, Fstimulus(3, 111) = 184.9, p < 0.0001, Ftreatment(3, 37) = 1.48, p = 0.24. PPI: Finteraction(6, 76) = 3.33, p = 0.0057, Fstimulus(2,76) = 105.7, p < 0.0001, Ftreatment(3, 38) = 4.78, p = 0.0064; two-way RM ANOVA, Tukey’s post-hoc test was used for multiple comparisons). In all figures, *p < 0.05; ***p < 0.001.

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