Rosen G D, Waters N S, Galaburda A M, Denenberg V H
Dyslexia Research Laboratory, Beth Israel Hospital, Boston, MA 02215, USA.
Brain Res. 1995 May 29;681(1-2):177-89. doi: 10.1016/0006-8993(95)00312-e.
Several strains of autoimmune mice spontaneously develop molecular layer ectopias that are similar in appearance to those seen in humans and are caused by disturbances in neocortical neuronal migration. These mice also exhibit behavioral anomalies, some of which correlate with ectopias, others with the immunological disorder. In this study, we induced neocortical ectopias (via puncture wounds) and microgyria (via freezing lesions) in the neocortex of 1-day-old (newborn) mice without immune disorders in an attempt to further disentangle the effects of autoimmunity and of cortical malformation on behavior. In addition, we wished to compare the behavioral effects of small ectopias to larger microgyric lesions. DBA mice were assigned at birth to receive either a puncture wound or freezing lesion of either the left or right hemisphere. An independent group was subjected to sham surgery. In adulthood, these mice were given a battery of tests designed to measure lateralization and learning capacity. Lesioned mice (irrespective of hemisphere or type of damage) performed poorly when compared to sham-operated animals in discrimination learning, in a spatial Morris Maze Match-to-Sample task, and in a Lashley Type III maze. In shuttlebox avoidance conditioning, where immunological disorder has been shown to compromise behavioral performance in autoimmune mice, there was no difference between lesioned and sham animals. These results (1) support the dissociation between the effects of developmental neocortical anomalies and autoimmune disease on behavior (2) reveal similarities between spontaneous and induced neocortical malformations and (3) fail to support a difference in behavioral effects between ectopias and microgyria.
几种自身免疫性小鼠品系会自发出现分子层异位，其外观与人类所见相似，由新皮质神经元迁移紊乱引起。这些小鼠还表现出行为异常，其中一些与异位有关，另一些与免疫紊乱有关。在本研究中，我们在1日龄（新生）无免疫紊乱的小鼠新皮质中诱导新皮质异位（通过穿刺伤口）和微小脑回（通过冷冻损伤），试图进一步厘清自身免疫和皮质畸形对行为的影响。此外，我们希望比较小异位与较大微小脑回损伤的行为效应。DBA小鼠在出生时被分配接受左半球或右半球的穿刺伤口或冷冻损伤。一个独立的组接受假手术。成年后，对这些小鼠进行一系列旨在测量偏侧化和学习能力的测试。与假手术动物相比，损伤小鼠（无论半球或损伤类型）在辨别学习、空间莫里斯水迷宫样本匹配任务和拉什利III型迷宫中表现较差。在穿梭箱回避条件反射中，已证明免疫紊乱会损害自身免疫性小鼠的行为表现，损伤小鼠和假手术小鼠之间没有差异。这些结果（1）支持发育性新皮质异常和自身免疫性疾病对行为的影响之间的分离（2）揭示自发和诱导的新皮质畸形之间的相似性（3）不支持异位和微小脑回在行为效应上的差异。
