Soumiya Hitomi, Godai Ayumi, Araiso Hiromi, Mori Shingo, Furukawa Shoei, Fukumitsu Hidefumi
Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
PLoS One. 2016 Jun 30;11(6):e0158583. doi: 10.1371/journal.pone.0158583. eCollection 2016.
Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD). While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice) and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age-matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation.
触觉感知异常，如感觉防御，是自闭症谱系障碍（ASD）的常见特征。虽然不是ASD的诊断标准，但触觉感知缺陷导致了所观察到的社交沟通技能缺失。然而，触觉感知缺陷对社交行为发展的影响仍不确定，对与社交互动情绪调节相关的神经回路的影响也不确定。在新生啮齿动物中，触须是最重要的触觉器官，因此双侧触须修剪被用作早期触觉剥夺的模型。为了研究触觉剥夺对成年行为的影响，我们在出生后10天对小鼠进行双侧触须修剪（BWT10小鼠），并在触须完全再生后检查成年小鼠的社交行为、触觉辨别能力以及神经激活标志物c-Fos的表达。成年BWT10小鼠在跨越间隙测试中的可跨越距离明显短于年龄匹配的对照组，表明依赖触须的触觉感知持续存在缺陷。与对照组不同，BWT10小鼠在三室测试中对含有同种个体的社交隔室没有偏好。此外，BWT10小鼠杏仁核回路的发育受到严重影响。根据c-Fos的表达模式，在BWT10杏仁核回路中发现，在依赖触须的线索学习过程中，处理对高度应激的恐惧/焦虑相关反应时出现多动，但在处理奖励刺激的回路中没有。这些结果表明，新生小鼠触须修剪及随之而来的依赖触须的触觉辨别能力受损会严重干扰杏仁核依赖的情绪调节的发展。
