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IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.

Yasumura M, Yoshida T, Yamazaki M, Abe M, Natsume R, Kanno K, Uemura T, Takao K, Sakimura K, Kikusui T, Miyakawa T, Mishina M - Sci Rep (2014)

Bottom Line: Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACT
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

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Deficit of spatial working memory in IL1RAPL1 knockout mice.(A–D) Eight-arm radial maze test of wild-type (open circles and white bars, n = 19) and IL1RAPL1 knockout mice (closed circles and black bars, n = 20). Different arm choices among the first 8 arms (A and C), and total number of arms revisited (B and D) were recorded. During 25–30th training, a delay was applied after the first 4 pellets were consumed (C and D). Data are presented as average of 2 trials. (E and F) The percentage of correct responses in T-maze forced alternation task of wild-type (open circles and white bars, n = 40) and IL1RAPL1 knockout mice (closed circles and black bars, n = 40). Delays were applied in order of 3, 3, 10, 30, 60, 3, 3, 10, 30 and 60 s per session (F). (G) The percentage of correct responses in T-maze left/right discrimination task of wild-type (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). After session 10, the baited arm was changed to the other side. All values represent as mean ± SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; two-way repeated measures ANOVA followed by Fisher's LSD test (E and G). The p values indicate genotype effect in two-way repeated measures ANOVA (E and G).
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f3: Deficit of spatial working memory in IL1RAPL1 knockout mice.(A–D) Eight-arm radial maze test of wild-type (open circles and white bars, n = 19) and IL1RAPL1 knockout mice (closed circles and black bars, n = 20). Different arm choices among the first 8 arms (A and C), and total number of arms revisited (B and D) were recorded. During 25–30th training, a delay was applied after the first 4 pellets were consumed (C and D). Data are presented as average of 2 trials. (E and F) The percentage of correct responses in T-maze forced alternation task of wild-type (open circles and white bars, n = 40) and IL1RAPL1 knockout mice (closed circles and black bars, n = 40). Delays were applied in order of 3, 3, 10, 30, 60, 3, 3, 10, 30 and 60 s per session (F). (G) The percentage of correct responses in T-maze left/right discrimination task of wild-type (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). After session 10, the baited arm was changed to the other side. All values represent as mean ± SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; two-way repeated measures ANOVA followed by Fisher's LSD test (E and G). The p values indicate genotype effect in two-way repeated measures ANOVA (E and G).

Mentions: We next examined the spatial working memory by the eight-arm radial maze and T-maze tests. Both tests were performed with food-restricted mice, using food pellets as a reward. In the eight-arm radial maze test, there were no significant differences between wild-type and IL1RAPL1 knockout mice in the number of different arm choices among the first 8 entries (genotype effect, F1, 37 = 1.87, p = 0.2; genotype × block of trials effect, F11, 407 = 0.83, p = 0.6, repeated measures ANOVA) (Fig. 3A) and the total number of revisiting errors in which the mice returned to the arms that had been visited previously to retrieve a food pellet (genotype effect, F1, 37 = 3.39, p = 0.07; genotype × block of trials effect, F11, 407 = 0.33, p = 0.98) (Fig. 3B). We then examined the eight-arm radial maze test with a delay time. The number of different arm choices was significantly smaller in IL1RAPL1 knockout mice than in wild-type mice (Fig. 3C: genotype effect, F1, 37 = 6.44, p = 0.02; genotype × block of trials effect, F2, 74 = 0.58, p = 0.6) and that of revisiting errors was significantly larger in knockout mice (Fig. 3D: genotype effect, F1, 37 = 4.94, p = 0.03; genotype × block of trials effect, F2, 74 = 0.003, p = 1.0). These results suggest that the spatial working memory was mildly impaired in IL1RAPL1 knockout mice.


IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.

Yasumura M, Yoshida T, Yamazaki M, Abe M, Natsume R, Kanno K, Uemura T, Takao K, Sakimura K, Kikusui T, Miyakawa T, Mishina M - Sci Rep (2014)

Deficit of spatial working memory in IL1RAPL1 knockout mice.(A–D) Eight-arm radial maze test of wild-type (open circles and white bars, n = 19) and IL1RAPL1 knockout mice (closed circles and black bars, n = 20). Different arm choices among the first 8 arms (A and C), and total number of arms revisited (B and D) were recorded. During 25–30th training, a delay was applied after the first 4 pellets were consumed (C and D). Data are presented as average of 2 trials. (E and F) The percentage of correct responses in T-maze forced alternation task of wild-type (open circles and white bars, n = 40) and IL1RAPL1 knockout mice (closed circles and black bars, n = 40). Delays were applied in order of 3, 3, 10, 30, 60, 3, 3, 10, 30 and 60 s per session (F). (G) The percentage of correct responses in T-maze left/right discrimination task of wild-type (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). After session 10, the baited arm was changed to the other side. All values represent as mean ± SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; two-way repeated measures ANOVA followed by Fisher's LSD test (E and G). The p values indicate genotype effect in two-way repeated measures ANOVA (E and G).
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Related In: Results  -  Collection

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f3: Deficit of spatial working memory in IL1RAPL1 knockout mice.(A–D) Eight-arm radial maze test of wild-type (open circles and white bars, n = 19) and IL1RAPL1 knockout mice (closed circles and black bars, n = 20). Different arm choices among the first 8 arms (A and C), and total number of arms revisited (B and D) were recorded. During 25–30th training, a delay was applied after the first 4 pellets were consumed (C and D). Data are presented as average of 2 trials. (E and F) The percentage of correct responses in T-maze forced alternation task of wild-type (open circles and white bars, n = 40) and IL1RAPL1 knockout mice (closed circles and black bars, n = 40). Delays were applied in order of 3, 3, 10, 30, 60, 3, 3, 10, 30 and 60 s per session (F). (G) The percentage of correct responses in T-maze left/right discrimination task of wild-type (open circles, n = 40) and IL1RAPL1 knockout mice (closed circles, n = 40). After session 10, the baited arm was changed to the other side. All values represent as mean ± SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001, respectively; two-way repeated measures ANOVA followed by Fisher's LSD test (E and G). The p values indicate genotype effect in two-way repeated measures ANOVA (E and G).
Mentions: We next examined the spatial working memory by the eight-arm radial maze and T-maze tests. Both tests were performed with food-restricted mice, using food pellets as a reward. In the eight-arm radial maze test, there were no significant differences between wild-type and IL1RAPL1 knockout mice in the number of different arm choices among the first 8 entries (genotype effect, F1, 37 = 1.87, p = 0.2; genotype × block of trials effect, F11, 407 = 0.83, p = 0.6, repeated measures ANOVA) (Fig. 3A) and the total number of revisiting errors in which the mice returned to the arms that had been visited previously to retrieve a food pellet (genotype effect, F1, 37 = 3.39, p = 0.07; genotype × block of trials effect, F11, 407 = 0.33, p = 0.98) (Fig. 3B). We then examined the eight-arm radial maze test with a delay time. The number of different arm choices was significantly smaller in IL1RAPL1 knockout mice than in wild-type mice (Fig. 3C: genotype effect, F1, 37 = 6.44, p = 0.02; genotype × block of trials effect, F2, 74 = 0.58, p = 0.6) and that of revisiting errors was significantly larger in knockout mice (Fig. 3D: genotype effect, F1, 37 = 4.94, p = 0.03; genotype × block of trials effect, F2, 74 = 0.003, p = 1.0). These results suggest that the spatial working memory was mildly impaired in IL1RAPL1 knockout mice.

Bottom Line: Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACT
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Show MeSH
Related in: MedlinePlus