Reciprocal alterations in pre- and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia.
Reciprocal alterations in pre- and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia.
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DOI：
10.1093/cercor/12.10.1063
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发表时间：
2002-10
期刊：
影响因子：
3.7
通讯作者：
D. Volk;J. Pierri;J. Fritschy;S. Auh;A. Sampson;D. Lewis
中科院分区：
文献类型：
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作者：
D. Volk;J. Pierri;J. Fritschy;S. Auh;A. Sampson;D. Lewis
在精神分裂症患者的前额皮质中，GABA 合成和再摄取的标记物似乎在包括吊灯细胞在内的中间神经元子集中发生了选择性改变。确定突触前 GABA 标记物的这些干扰对抑制信号传导的影响需要了解吊灯细胞突触后目标（锥体神经元的轴突初始段 (AIS)）处 GABA(A) 受体的状态。由于 GABA(A) 受体的 α(2) 亚基优先定位于锥体神经元 AIS，因此我们对来自 14 名匹配的三联体精神分裂症受试者、重度抑郁症受试者和对照受试者的包含前额皮质区域 46 的组织切片中的 α(2) 亚基免疫反应性 AIS 进行了定量。系统随机抽样显示，与对照受试者相比，精神分裂症受试者中每 mm(2) α(2) 标记的 AIS 的平均数量显着增加 (P = 0.007) 113%，与重度抑郁症受试者相比则无显着增加。此外，在精神分裂症受试者中，α(2) 标记的 AIS 密度与 GABA 膜转运蛋白免疫反应的吊灯轴突末端密度呈负相关（r = -0.49，P = 0.038）。这些数据表明，由于精神分裂症患者吊灯轴突末端的 GABA 神经传递缺陷，锥体神经元 AIS 的 GABA(A) 受体上调。因此，吊灯神经元-锥体神经元突触的抑制紊乱可能是精神分裂症前额皮质功能障碍的关键组成部分。
In the prefrontal cortex of subjects with schizophrenia, markers of the synthesis and re-uptake of GABA appear to be selectively altered in a subset of interneurons that includes chandelier cells. Determining the effect of these disturbances in presynaptic GABA markers on inhibitory signaling requires knowledge of the status of GABA(A) receptors at the postsynaptic targets of chandelier cells, the axon initial segments (AIS) of pyramidal neurons. Because the alpha(2) subunit of the GABA(A) receptor is preferentially localized at pyramidal neuron AIS, we quantified alpha(2) subunit immunoreactive AIS in tissue sections containing prefrontal cortex area 46 from 14 matched triads of subjects with schizophrenia, subjects with major depression and control subjects. Systematic, random sampling revealed that the mean number of alpha(2)-labeled AIS per mm(2) in subjects with schizophrenia was significantly (P = 0.007) increased by 113% compared to control subjects and non-significantly increased compared to subjects with major depression. Furthermore, within subjects with schizophrenia, the density of alpha(2)-labeled AIS was negatively correlated (r = -0.49, P = 0.038) with the density of chandelier axon terminals immunoreactive for the GABA membrane transporter. These data suggest that GABA(A) receptors are up-regulated at pyramidal neuron AIS in response to deficient GABA neuro-transmission at chandelier axon terminals in schizophrenia. Thus, disturbances in inhibition at the chandelier neuron-pyramidal neuron synapse may be a critical component of prefrontal cortical dysfunction in schizophrenia.