The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input
Fig 6
LC/NE neurons are activated by inputs from dmPFC and TeA, and project to dmPFC.
(A) (Left) Experimental paradigm for examining major brain regions that project to LC, using retrobeads (red) injected in the LC. (Right) Brain regions with red fluorescence, dmPFC and TeA. Scale bar, 200 μm. (B) Responses of the LC neurons in LC slice to opto-activation of axonal terminals from TeA neurons (red bar, 10 s). rAAV2/9-CaMKII-ChR2-mCherry virus injected in the TeA, and laser illumination in the slices. Scale bars, 20 pA and 5 s. (C) (Left) Representative responses of LC neurons to opto-activation (bar, 50 ms) of axonal terminals from either T-neurons or S-neurons. Scale bars, 20 pA and 50 ms. (Right) All LC neurons responded to opto-activation of axonal terminals from the T-neurons, but none responded to opto-activation of axonal terminals from the S-neurons. n = 10 cells. (D) (Left) Experimental paradigm for examining outputs from the LC neurons receiving dmPFC projections. (Right) Presence of the mCherry fluorescence (red) in the dmPFC but not LA or BLA. Scale bars, 200 μm. (E) (Left) Schematic diagram showing opto-activation of dmPFC neurons axon terminals and recording in the dmPFC-projecting LC neurons in LC slices. (Right) 71% of dmPFC-projecting LC neurons responded to opto-activation of dmPFC neuron axon terminals and 29% showed no response to the same stimuli. (F) (Left) Diagram for virus injections, (middle and right) Ca2+ responses elicited by 30 s CS+, 30 s CS−, 10 s CS+ and 2 s CS+ in the LC neurons receiving dmPFC inputs. Scale bars, 0.5% ΔF/F and 10 s. N = 7 mice. Insert: AUC of ΔF/F of Ca2+ signals. Two-tailed unpaired t test, 30 s CS+ vs. 30 s CS−, P < 0.001; 10 s CS+ vs. 2 s CS+, P < 0.05. (G) (Left) Diagram for virus injections, (middle and right) Ca2+ responses to 30 s CS+, 30 s CS−, 10 s CS+ and 2 s CS+ in the LC neurons projecting to dmPFC. Scale bars, 0.5% ΔF/F and 10 s. N = 7 mice. Insert: AUC of ΔF/F of Ca2+ signals. Two-tailed unpaired t test, 30 s CS+ vs. 30 s CS−, P < 0.001; 10 s CS+ vs. 2 s CS+, P < 0.05.