Figure 5. PSD-95 knockdown in infralimbic cortex impairs remote fear memory retrieval.

(a) Example of green fluorescent protein (GFP) localization of the PSD-95 knockdown adenoassociated virus in the IL (scale bar=200 µm). (b) Example Western blots showing viral-induced knockdown of PSD-95 protein. (c) Schematic of experimental design for testing recent and remote retrieval of a cued fear memory. (d) IL PSD-95 KD mice showed less freezing than GFP-virus controls during remote, but not recent retrieval (n=12–17). (e) ACC PSD-95 KD mice showed similar freezing levels to GFP controls during recent and remote retrieval (n=9–11). Inset: example of GFP localization of the PSD-95 KD adenoassociated virus in the Cg1 region of the ACC (scale bar=200 µm). (f) Schematic of experimental design for testing fear extinction. (g) IL PSD-95 KD mice decreased freezing from the first to the last extinction trial-block, but less so than GFP-virus controls. GFP-virus controls, but not IL PSD-95 KD mice, froze less during extinction retrieval as compared to the first trial-block of extinction training (n=7–9). (h) Example images of dendritic spines in IL pyramidal neurons from a PSD-95 KD (top) and GFP control (bottom) (scale bar=15 µm). (i) Examples and cartoon showing examples of narrow (N) and wide (W) subpopulations of dendritic spines. (j,k) PSD-95 KD decreased the spine head width, but not density, of relatively wide spines on IL pyramidal neurons, relative to GFP controls (n=7 mice per group, n=15–23 cells per group). Data are means ±SEM. *P<.05 vs. PSD-95 KD/same time point or spine subpopulation