Perineuronal Nets in the Dorsomedial Striatum Contribute to Behavioral Dysfunction in Mouse Models of Excessive Repetitive Behavior.
Perineuronal Nets in the Dorsomedial Striatum Contribute to Behavioral Dysfunction in Mouse Models of Excessive Repetitive Behavior.
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DOI：
10.1016/j.bpsgos.2021.11.005
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发表时间：
2022-10
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影响因子：
--
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中科院分区：
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过度重复行为是几种神经精神疾病的衰弱症状。背侧纹状体中的小清蛋白阳性抑制性中间神经元与重复行为有关，并且这些细胞的相当大的一部分被神经元周网（PNN），特化的细胞外基质结构包围。虽然PNN与可塑性和神经精神疾病有关，但以前没有研究调查过它们与过度重复行为的关系。我们使用组织化学和共聚焦成像研究了4种过度重复行为小鼠模型（BTBR、Cntnap 2、Shank 3、产前丙戊酸盐治疗）背侧纹状体中小清蛋白阳性细胞周围的PNN。然后，我们研究了这些模型之一，BTBR小鼠，详细地，与DiI标记，在体内和体外记录，和行为分析。接下来，我们使用软骨素酶ABC降解背内侧纹状体（DMS）中的PNN，并评估树突棘密度、电生理学和重复行为。我们发现，与对照组小鼠相比，在所有4种过度重复行为小鼠模型的DMS中，具有PNN的小清蛋白阳性中间神经元的百分比更大。在BTBR小鼠中，我们发现较少的树突棘中棘神经元（小白蛋白阳性interneurons的目标）和神经元振荡的差异，以及抑制性突触后电位与对照小鼠相比。在BTBR小鼠中减少DMS PNN改变了树突棘密度和抑制反应以及正常化的重复行为。这些发现表明，DMS中的细胞异常与适应不良的重复行为有关，并且操纵PNN可以恢复正常水平的重复行为，同时改变DMS树突棘和抑制信号。
Excessive repetitive behavior is a debilitating symptom of several neuropsychiatric disorders. Parvalbumin-positive inhibitory interneurons in the dorsal striatum have been linked to repetitive behavior, and a sizable portion of these cells are surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures. Although PNNs have been associated with plasticity and neuropsychiatric disease, no previous studies have investigated their involvement in excessive repetitive behavior. We used histochemistry and confocal imaging to investigate PNNs surrounding parvalbumin-positive cells in the dorsal striatum of 4 mouse models of excessive repetitive behavior (BTBR, Cntnap2, Shank3, prenatal valproate treatment). We then investigated one of these models, the BTBR mouse, in detail, with DiI labeling, in vivo and in vitro recordings, and behavioral analyses. We next degraded PNNs in the dorsomedial striatum (DMS) using the enzyme chondroitinase ABC and assessed dendritic spine density, electrophysiology, and repetitive behavior. We found a greater percentage of parvalbumin-positive interneurons with PNNs in the DMS of all 4 mouse models of excessive repetitive behavior compared with control mice. In BTBR mice, we found fewer dendritic spines on medium spiny neurons (targets of parvalbumin-positive interneurons) and differences in neuronal oscillations as well as inhibitory postsynaptic potentials compared with control mice. Reduction of DMS PNNs in BTBR mice altered dendritic spine density and inhibitory responses and normalized repetitive behavior. These findings suggest that cellular abnormalities in the DMS are associated with maladaptive repetitive behaviors and that manipulating PNNs can restore normal levels of repetitive behavior while altering DMS dendritic spines and inhibitory signaling.
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DOI：
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发表时间：
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