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Fig. 4 | Molecular Autism

Fig. 4

From: CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes

Fig. 4

CYFIP1-overexpressing mice show increased fear in contextual and cued fear conditioning but do not demonstrate sensory processing deficits. a Schematic of fear conditioning protocol. Learning and memory of aversive stimuli was assessed using trace and contextual fear conditioning. b On day 1, freezing was recorded as mice were conditioned to a tone using a series of 3, 80-dB tones followed by 0.5-mA shocks. While all mice acquired the tone/shock association, there was a significant increase in freezing in the Tg #2 mice compared to their WT littermates during this acquisition phase. This increase in freezing was not observed in Tg #1 mice. c Tg #2 mice demonstrated an increase in freezing in the shock context which persisted when they were introduced to a novel context. There was no increase in freezing observed in the Tg #1 mice in the shock or novel contexts (Shock context: Line 1 WT = 70.91 ± 3.242, Tg #1, 69.69 ± 4.291. Line 2 WT = 44.78 ± 2.596, Tg #2, 53.54 ± 3.098. Novel context: Line 1 WT = 40.76 ± 4.613, Tg #1 = 45.89 ± 4.431. Line 2 WT, 26.27 ± 2.497, Tg #2, 35.87 ± 2.976). d Tg #1 mice showed a significant increase in freezing in response to the tone, and Tg #2 mice showed a significant increase in freezing in the intertone interval (Tone: Line 1 WT = 64.28 ± 3.793, Tg #1 = 74.37 ± 2.962. Line 2 WT = 44.04 ± 3.759, Tg #2, 54.68 ± 4.09. Intertone interval: Line 1 WT = 50.12 ± 4.585, Tg #1 = 56.38 ± 4.076. Line 2 WT = 29.84 ± 3.128, Tg #2, 41.67 ± 3.121). e The thermal pain reflex of Tg mice was assessed using the hot plate assay. The latency to paw withdrawal was similar in Tg and WT littermates (Line 1 WT = 15.05 ± 1.35, Tg #1 = 13.88 ± 0.65. Line 2 WT = 11.29 ± 0.92, Tg # 2 = 12.65 ± 1.13). f Sensory gating was assessed using the PPI test. Tg mice showed no differences in PPI at 70, 75, and 80 dBs compared to WT (70 dB: Line 1 WT = 48.11 ± 3.18, Tg #1 = 42.93 ± 3.57. Line 2 WT = 45.21 ± 3.63, Tg #2 = 43.40 ± 4.09. 75 dB: Line 1 WT = 71.37 ± 2.22, Tg #1 = 70.10 ± 2.65. Line 2 WT = 62.69 ± 2.66, Tg #2 = 62.97 ± 2.74. 80 dB: Line 1 WT = 77.20 ± 1.68, Tg #1 = 79.14. Line 2 WT = 74.19 ± 2.37, Tg #2 = 70.28 ± 1.83). CYFIP1 (g) mRNA and h protein levels in the basolateral amygdala were significantly increased in both Tg lines. NS, not significant. *p < 0.05. **p < 0.01. ***p < 0.001. ****p < 0.0001. See Additional file 3: Table S3 n’s

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