Israelashvili Michal, Yael Dorin, Vinner Esther, Belelovsky Katya, Bar-Gad Izhar
The Leslie & Susan Goldschmied (Gonda) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
The Leslie & Susan Goldschmied (Gonda) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
Cortex. 2020 Jun;127:231-247. doi: 10.1016/j.cortex.2020.02.010. Epub 2020 Feb 29.
Tourette syndrome (TS) and attention deficit hyperactivity disorder (ADHD) are two neurodevelopmental hyper-behavioral disorders that are highly comorbid. The source of this comorbidity and the neuronal mechanisms underlying these disorders are still unclear. We examined the neuronal activity of freely behaving rats before and after striatal disinhibition, to reveal the similar and distinct neuronal components underlying the mechanisms of TS-like and ADHD-like symptom expression. Focal disinhibition induced motor tics, locomotor hyperactivity or a comorbid effect depending on the location of the injection within the different functional domains of the striatum. While injections within the motor domain induced motor tics, injections into the limbic domain induced mainly locomotor hyperactivity. Disinhibition, regardless of its striatal location, led to qualitatively similar macro-scale and micro-scale neuronal changes. These changes were localized to the domain of the manipulation and remained partly segregated, indicating that hyperactivity is induced as a result of changes in the limbic domain without directly activating the motor domain. Despite the general similarity of induced neuronal changes, these changes were associated with different behavioral effects and were more stereotypic and pronounced following motor-domain disinhibition in comparison to limbic-domain disinhibition. Our recordings revealed a disparity in the neuronal input-output transformation of the two models of the disorders. The results suggest that tic expression and hyperactivity states share similar local neuronal activity changes which manifest in different neuronal and behavioral outcomes. These results expose an intriguing link between tics and their comorbid symptoms and hint at striatal disinhibition, resulting from GABAergic alterations, as a potential common mechanism underlying distinct symptoms expressed by hyper-behavioral patients.
抽动秽语综合征（TS）和注意力缺陷多动障碍（ADHD）是两种高度共病的神经发育性多动行为障碍。这种共病的根源以及这些障碍背后的神经元机制仍不清楚。我们检查了自由活动大鼠在纹状体去抑制前后的神经元活动，以揭示抽动秽语综合征样和注意力缺陷多动障碍样症状表达机制中相似和不同的神经元成分。局部去抑制根据注射在纹状体不同功能域内的位置诱导运动抽动、运动亢进或共病效应。虽然在运动域内注射会诱导运动抽动，但向边缘域内注射主要诱导运动亢进。无论在纹状体的哪个位置进行去抑制，都会导致在宏观尺度和微观尺度上性质相似的神经元变化。这些变化局限于操作区域，并且部分保持分离，这表明运动亢进是由边缘域的变化引起的，而没有直接激活运动域。尽管诱导的神经元变化总体相似，但这些变化与不同的行为效应相关，并且与边缘域去抑制相比，运动域去抑制后这些变化更具刻板性且更明显。我们的记录揭示了这两种障碍模型在神经元输入 - 输出转换方面的差异。结果表明，抽动表达和多动状态共享相似的局部神经元活动变化，这些变化表现为不同的神经元和行为结果。这些结果揭示了抽动与其共病症状之间的有趣联系，并暗示由GABA能改变导致的纹状体去抑制是多动行为患者所表现出的不同症状的潜在共同机制。
