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. 2021 Apr 1;10:e67267. doi: 10.7554/eLife.67267

Figure 4. IGF-1 facilitates the extinction memory by reducing mIAHP and sIAHP.

(A) (top) Image showing the infralimbic cortex (IL) localization. (bottom) Nissl-stained coronal section of rat IL, the orange arrow indicates the tip of the cannula implanted on the IL. (B) Plot showing the time course of the percentage of freezing during the extinction protocol for the three groups studied (saline, IGF-1, and NVP-+IGF-1). Saline (n = 11), IGF-1 (n = 14), and NVP-AEW541 +IGF-1 (n = 12) were directly applied into the IL through the implanted cannula 30 min before extinction training (day 3). The black arrow indicates the time of infusion. (*p<0.05 **p<0.01 saline vs IGF-1 and NPV + IGF-1 #p<0.05; ##p<0.01; ###p<0.001 IGF-1 vs NPV + IGF-1; One-way ANOVA with post hoc Tukey's multiple comparisons test). (C) Representative mIAHP and sIAHP current traces recorded in three groups of animals studied that showed fear extinction (D) Bar diagrams summarizing the mIAHP for all the groups studied. Recordings were performed in day 4 (test) after finishing the extinction protocol; saline (n = 11 cells/3 animals) vs IGF-1 (n = 7 cells/4 animals) *p<0.05; IGF-1 vs NPV + IGF-1 (n = 9 cells/3 animals) **p<0.01 and saline (n = 11 cells/3 animals) vs NPV + IGF-1 (n = 9 cells/3 animals) ns, one-way ANOVA with post hoc Tukey's multiple comparisons test. (E) Bar diagrams summarizing the sIAHP for all the groups studied. Saline (n = 11 cells/3 animals) vs IGF-1 (n = 7 cells/4 animals) *p<0.05; IGF-1 vs NPV + IGF-1 (n = 9 cells/3 animals) **p<0.01 and saline (n = 11 cells/3 animals) vs NPV + IGF-1 (n = 9 cells/3 animals) ns, one-way ANOVA with post hoc Tukey's multiple comparisons test. (F) For each rat in the extinction groups, the mIAHP and sIAHP for all cells were averaged. Across rats, these values were significantly correlated with freezing levels at test (r = 0.763 for mIAHP and r = 0.787 for sIAHP pointing to that the reduction in both currents is correlated with the extinction recall). (G) Representative traces recorded from IL-L5PNs from animals that showed fear extinction after 200 pA (left) current injection in saline (black); IGF-1 (red) and NVP + IGF-1 (gray). Frequency-injected current relationships for IL-L5PNs in saline (black, n = 10 cells/5 animals) IGF-1 (red, n = 7 cells/3 animals) and NVP + IGF-1 (gray, n = 6 cells/3 animals). (*) IGF-1 vs saline and (#) IGF-1 vs. NVP + IGF-1; one-way ANOVA with post hoc Tukey's multiple comparisons test. See also Figure 4—figure supplement 1 and Figure 4—figure supplement 2.

Figure 4—source data 1. Source data for Figure 4.
IGF-1 facilitates the extinction memory by reducing mIAHP and sIAHP.

Figure 4.

Figure 4—figure supplement 1. Protocol of behavior.

Figure 4—figure supplement 1.

(A) The experimental design of the conditioned fear experiments. (B) Plot showing the time course of the percentage of freezing during the experiment for the two groups studied: conditioned (COND, black circles; n = 7) and extinction (EXT, white circles; n = 11) groups. As expected, animals in the COND group showed higher levels of freezing to the test tones compared with the EXT groups (***p<0.001; **p<0.01; one-way ANOVA with post hoc Tukey's multiple comparisons test).
Figure 4—figure supplement 1—source data 1. Source data for Figure 4—figure supplement 1.
Protocol of behavior.
Figure 4—figure supplement 2. AHPs of the L5PN of the IL recorded from animals after fear extinction.

Figure 4—figure supplement 2.

(A) Bar diagram summarizing fAHP from rats NAÏVE (n = 10 cells/8 animals) and after test behaviors in different groups: EXT (n = 6 cells/2 animals); Ext-Saline (n = 10 cells/3 animals); Ext-IGF-1 (n = 7 cells/3 animals); Ext-NVP +IGF-1 (n = 8 cells/2 animals) One-way ANOVA with post hoc Turkey's multiple comparisons test *p<0.05; **p<0.01. (B) Bar diagram summarizing mAHP from rats NAÏVE (n = 16 cells/10 animals) and after test behaviors in different groups EXT (n = 6 cells/2 animals); Ext-Saline (n = 13 cells/5 animals); Ext-IGF-1 (n = 6 cells/3 animals); Ext-NVP +IGF-1 (n = 11 cells/3 animals) One-way ANOVA with post hoc Turkey's multiple comparisons test *p<0.05; **p<0.01. (C) Bar diagram summarizing sAHP from rats NAÏVE (n = 12 cells/6 animals) and after test behaviors in different groups EXT (n = 6 cells/2 animals); Ext-Saline (n = 11 cells/4 animals); Ext-IGF-1 (n = 6 cells/3 animals); Ext-NVP +IGF-1 (n = 11 cells/3 animals); one-way ANOVA with post hoc Turkey's multiple comparisons test *p<0.05. See also Supplementary file 1.
Figure 4—figure supplement 2—source data 1. Source data for Figure 4—figure supplement 2.
AHPs of the L5PN of the IL recorded from animals after fear extinction.