Research ArticleNEUROPSYCHOLOGY

Prefrontal inputs to the amygdala instruct fear extinction memory formation

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Science Advances  31 Jul 2015:
Vol. 1, no. 6, e1500251
DOI: 10.1126/sciadv.1500251

Figures

  • Fig. 1 Bidirectional control of the vmPFC-amygdala circuit.

    (A and C) Examples (top) and virus localization population heat maps representing all mice used in the current study (bottom; red and blue respectively represent maximum and minimum areas of cumulative virus localization across mice) of ChR2-AAV–expressing (A) and ArchT-AAV–expressing (C) glutamatergic neurons in vmPFC. Scale bar, 500 μm. (B and D) Raster plots and firing rate from single units (top), and z-scored population activity (bottom) showing blue-light (473 nm, 10 mW, 20 Hz, 5-ms pulses) increased (B) and green-light (532 nm, 10 mW, continuous) decreased (D) in vivo vmPFC unit activity in ChR2-AAV– and ArchT-AAV–expressing neurons. (E) Example of slice containing ChR2-AAV–expressing vmPFC axons in the BL and cartoon depicting the procedure for recording blue light–evoked activity at BL pyramidal neurons. (F) Blue light shone on ChR2-AAV–expressing vmPFC axons in the BL increased EPSC amplitude at BL pyramidal neurons in a light intensity–dependent manner (scale bar: y axis, 500 pA; x axis, 50 ms). (G) Application of the AMPA receptor blocker CNQX abolished light-evoked EPSCs at BL pyramidal neurons (scale bar: y axis, 300 pA; x axis, 50 ms). (H and J) Examples of infected axons immunolabeled with anti–green fluorescent protein (GFP)/Alexa 488 antibodies (green) in the BL and BM of ChR2-AAV–expressing (H) and ArchT-AAV–expressing (J) vmPFC projection neurons. ICNs are immunolabeled with anti–Forkhead box protein P2 (FoxP2)–tetramethyl rhodamine isothiocyanate (TRITC) antibodies (red) (scale bars, 100 μm). (I and K) Cartoon depicting optic-fiber placement (top) and localization (bottom) targeting ChR2-AAV–expressing (I) and ArchT-AAV–expressing (K) vmPFC axons, representing all mice used in the current study. Data are means ± SEM.

  • Fig. 2 vmPFC-amygdala circuit stimulation facilitates extinction formation.

    (A and B) Blue light shone on ChR2-AAV–expressing vmPFC axons in the amygdala during full (50-trial) extinction training (A) did not change freezing during training or subsequent (light-free) retrieval (B). (C and D) Light shone during partial (10-trial) extinction training (C) decreased freezing during (light-free) retrieval (D). (E and F) Light shone during retrieval [after partial (10-trial, light-free) extinction training] (E) did not alter freezing (F). For virus expression and optical fiber locations, see Fig. 1, A, H, and I. Extinction trial-block = 5 CS (conditioned stimulus) presentations.

  • Fig. 3 vmPFC-amygdala circuit silencing impairs extinction formation and BL recruitment.

    (A and B) Green light shone on ArchT-AAV–expressing vmPFC axons in the amygdala during extinction training (A) increased freezing during training or subsequent (light-free) retrieval (B). (C and D) Light shone during retrieval (after light-free extinction training) (C) did not alter freezing (D). (E to G) Green light shone during extinction training (E) decreased the number of Zif268+ cells in the LA (F) and BL (G) (example images shown on the right; scale bar, 50 μm). For virus expression and optical fiber locations, see Fig. 1, C, J, and K. Extinction trial-block = 5 CS presentations.

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