Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Department of Psychology, University of Western Ontario, London, ON, Canada.
Transl Psychiatry. 2023 Oct 18;13(1):321. doi: 10.1038/s41398-023-02629-6.
Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.
许多神经发育障碍，包括自闭症谱系障碍（ASD），与感觉处理和感觉运动门控的变化有关。听觉惊跳反应和惊跳前抑制（PPI）是分别用于评估感觉处理和感觉运动门控的广泛使用的转化测量方法。Cntnap2 敲除（KO）大鼠已被证明是 ASD 的有效模型，表现出核心症状，包括感觉处理障碍。在这里，我们使用一种新方法来评估 Cntnap2 KO 大鼠的惊跳和 PPI，该方法允许识别单独的缩放组件：惊跳缩放，即对给定声音的惊跳幅度变化，以及声音缩放，反映声音处理的变化。Cntnap2 KO 大鼠由于整体反应增加（惊跳缩放）和声音/反应曲线左移（声音缩放）而表现出增加的惊跳。在存在预脉冲的情况下，野生型大鼠由于惊跳缩放和声音缩放而表现出惊跳减少，而 Cntnap2 KO 大鼠表现出正常的惊跳缩放，但声音缩放受损，导致报告的 PPI 缺陷。这些结果证实了惊跳和预脉冲的声音缩放确实是两个独立的过程，只有后者在 Cntnap2 KO 大鼠中受损。由于惊跳缩放可能与运动输出有关，而声音缩放与声音处理有关，因此这种新方法揭示了前临床模型中 PPI 中断的可能原因的更多信息。
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