Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects.
Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects.
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DOI：
10.1038/mp.2013.152
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发表时间：
2014-01
影响因子：
11
通讯作者：
Lewis, D. A.
中科院分区：
文献类型：
--
作者：
Glausier, J. R.;Fish, K. N.;Lewis, D. A.
关键词：
精神分裂症的皮层回路功能障碍已经在许多不同的分辨率水平上进行了研究，但没有在网络组织的最基本单元-突触输入。需要多标记电子或共聚焦光学显微镜检查特定类型的突触输入，并应用这些方法来定量研究人类死后组织中的疾病相关变化由于技术原因是不可行的。我们最近开发了一种多标记共聚焦光显微镜的方法，使得系统的识别和量化的突触输入，和本地化这些输入的蛋白质的相对水平，在人类死后组织。我们应用这种方法来量化小白蛋白篮细胞（PVBC）的输入区9的背外侧前额叶皮层精神分裂症和匹配的对照组。组织切片用谷氨酸脱羧酶（GAD 65）的65 kD亚型、PV和GABAA受体α1亚基进行三重标记。PVBC轴突终接定义为PV/GAD 65双标记点，PVBC输入定义为与GABAA受体α1亚基点重叠的PVBC终接。精神分裂症患者的PVBC输入密度没有变化，但PVBC扣结中的PV蛋白水平较低。与先前的报道一致，这些发现表明精神分裂症中的PVBC功能障碍反映了这些细胞及其轴突末端的分子而非结构改变。
Cortical circuitry dysfunction in schizophrenia has been studied at many different levels of resolution, but not at the most basic unit of network organization—synaptic inputs. Multi-label electron or confocal light microscopy is required to examine specific types of synaptic inputs, and application of these methods to quantitatively study disease-related changes in human postmortem tissue has not been feasible for technical reasons. We recently developed a multi-label confocal light microscopic approach that makes possible the systematic identification and quantification of synaptic inputs, and of the relative levels of proteins localized to these inputs, in human postmortem tissue. We applied this approach to quantify parvalbumin basket cell (PVBC) inputs in area 9 of the dorsolateral prefrontal cortex from schizophrenia and matched comparison subjects. Tissue sections were triple-labeled for the 65 kD isoform of glutamic acid decarboxylase (GAD65), PV and the GABAA receptor α1 subunit. PVBC axonal boutons were defined as PV/GAD65 dual-labeled puncta, and PVBC inputs were defined as a PVBC bouton that overlapped a GABAA receptor α1 subunit punctum. The density of PVBC inputs was unchanged in subjects with schizophrenia, but levels of PV protein were lower in PVBC boutons. In concert with prior reports, these findings indicate that PVBC dysfunction in schizophrenia reflects molecular and not structural alterations in these cells and their axon terminals.
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影响因子：
7.6
作者：
Glausier, Jill R.;Lewis, David A.
通讯作者：
Lewis, David A.
DOI：
10.1073/pnas.0609440103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Cho, R. Y.;Konecky, R. O.;Carter, C. S.
通讯作者：
Carter, C. S.
影响因子：
2.9
作者：
Fish, Kenneth N.;Sweet, Robert A.;Deo, Anthony J.;Lewis, David A.
通讯作者：
Lewis, David A.
DOI：
10.1523/jneurosci.0306-13.2013
发表时间：
2013-05-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fish KN;Hoftman GD;Sheikh W;Kitchens M;Lewis DA
通讯作者：
Lewis DA
影响因子：
5.3
作者：
Huang, Hsien-Sung;Matevossian, Anouch;Akbarian, Schahram
通讯作者：
Akbarian, Schahram