1 J. Neurosci。2002年2月22日:1290-302
PMID 11850457
Title I(H)通道有助于中脑中鉴定出的多巴胺能亚群的不同功能特性。
Abstract 黑质Nigra(SN)和腹侧对盖区(VTA)中的多巴胺能(DA)中脑神经元参与了各种大脑功能,例如自愿运动和奖励,并且是帕金森氏病和帕金森氏病和诸如疾病的靶标精神分裂症。To study the functional properties of identified DA neurons in mouse midbrain slices, we combined patch-clamp recordings with either neurobiotin cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT-PCR. We discriminated four DA subpopulations based on anatomical and neurochemical differences: two calbindin D28-k (CB)-expressing DA populations in the substantia nigra (SN/CB+) or ventral tegmental area (VTA/CB+), and respectively, two calbindin D28-k negative DA populations (SN/CB-, VTA/CB-). VTA/CB+ DA neurons displayed significantly faster pacemaker frequencies with smaller afterhyperpolarizations compared with other DA neurons. In contrast, all four DA populations possessed significant differences in I(h) channel densities and I(h) channel-mediated functional properties like下垂按以下顺序进行振幅和反弹延迟:sn/cb---> vta/cb---> sn/cb+ - > vta/cb+。单细胞RT-Multiplex PCR实验表明,差异钙蛋白素但无钙蛋白素的表达与差异I(H)通道密度相关。但是,只有在SN/CB- DA神经元中,I(H)通道才积极参与起搏器频率控制。总之,DA系统内的多样性不仅限于独特的轴突投影和突触连通性的差异,而且还涉及神经化学上和地形上不同DA神经元之间突触后电导的差异。
SCZ Keywords 精神分裂症, schizophrenic
2 PLoS ONE 2013 -1 8: e70553
PMID 23950961
Title 快速刺激性中间神经元的电生理异质性:枝形吊灯与篮细胞。
Abstract 在前额叶皮层中,白蛋白阳性抑制性神经元在延伸工作记忆的神经回路中起着重要作用,这些神经元的改变有助于病理生理精神分裂症。通常认为两种靶向锥体神经元,枝形吊灯细胞(CHC)和篮细胞(BCS)(BCS)的细胞蛋白蛋白神经元的形态不同类别,通常被认为具有相同的“快速加速”表型,其特征是短的动作电位。和高频发射没有适应。然而,来自不同物种的研究的发现表明,这两个细胞类别之间的某些电生理膜特性可能有所不同。在这项研究中,我们评估了快速刺激性中间神经元的生理异质性,这是两个因素的函数:物种(猕猴与大鼠)和形态学(吊灯与篮子)。我们先前表明,这两个物种之间的电生理膜特性不同。在这里,我们首次报告了猴子和大鼠之间CHCS膜性质的差异。我们还发现,许多膜特性将CHC与BCS区分开。这些差异中的一些是无关的(例如,快速和中等的过度过度,发射频率和去极化下垂), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species.
SCZ Keywords 精神分裂症, schizophrenic
3 欧元。J. Neurosci。2014年4月39日:1074-90
PMID 24712988
Title CA1锥体神经元的神经生理修饰在表达截短形式的s骨中断形式的转基因小鼠中。
Abstract a t(1; 11)平衡染色体易位在大型苏格兰家族中的盘状基因,并产生全基因组的联系精神分裂症和复发性重度抑郁症。这项研究描述了我们对转基因小鼠(DISC1TR)海马区域CA1中神经生理功能的体外研究,该研究表达了disc1的截断版本,旨在重现苏格兰T(1; 11)谱系中遗传状况的各个方面。我们在体外采用了斑板夹和细胞外记录方法,以比较圆盘动物和野生型同窝仔之间的内在特性和突触功能以及可塑性。CA1锥体神经元(CA1-PN)的斑块钳分析显示,多个亚阈值参数中没有基因型依赖性,包括静息势,输入抗性,超极化激活'下垂'和共振属性。近路刺激显示动作电位(AP)波形没有变化,尽管Disc1tr小鼠的AP产生速率较高。在50 hz的5-25 AP训练后,在倒闭的超极化电位中未观察到差异。Schaffer侧外(SC)途径中突触反应的贴片钳分析表明,配对脉冲促进,兴奋性突触后潜在求和或AMPA/NMDA比没有基因型依赖性。细胞外记录还显示出对SC突触反应的变化,并且在颞(TA)输入中也没有改变指示的输入输出和短期可塑性。然而,在Disc1tr小鼠中,SC途径中theta爆发引起的长期增强增强了,但在TA途径中完全丢失。这些数据表明,表达disc1的截断形式会影响CA1-PNS的内在特性,并对长期突触可塑性产生途径特异性影响。
SCZ Keywords 精神分裂症, schizophrenic
4 Physiol Rep 2014 5月2日:-1
PMID 24844635
Title Activation of 5-HT2A receptors by TCB-2 induces recurrent oscillatory burst discharge in layer 5 pyramidal neurons of the mPFC in vitro.
Abstract The medial prefrontal cortex (mPFC) is a region of neocortex that plays an integral role in several cognitive processes which are abnormal in精神分裂症病人。与其他皮层区域,large-bodied layer 5 pyramidal neurons serve as the principle subcortical output of microcircuits of the mPFC. The coexpression of both inhibitory serotonin 5-HT1A receptors on the axon initial segments, and excitatory 5-HT2A receptors throughout the somatodendritic compartments, by layer 5 pyramidal neurons allows serotonin to provide potent top-down regulation of input-output relationships within cortical microcircuits. Application of 5-HT2A agonists has previously been shown to enhance synaptic input to layer 5 pyramidal neurons, as well as increase the gain in neuronal firing rate in response to increasing depolarizing current steps. Using whole-cell patch-clamp recordings obtained from layer 5 pyramidal neurons of the mPFC of C57/bl6 mice, the aim of our present study was to investigate the modulation of long-term spike trains by the selective 5-HT2A agonist TCB-2. We found that in the presence of synaptic blockers, TCB-2 induced recurrent oscillatory bursting (ROB) after 15-20 sec of tonic spiking in 7 of the 14 cells. In those seven cells, ROB discharge was accurately predicted by the presence of a voltage下垂in response to a hyperpolarizing current injection. This effect was reversed by 5-10 min of drug washout and ROB discharge was inhibited by both synaptic activity and coapplication of the 5-HT2A/2C antagonist ketanserin. While the full implications of this work are not yet understood, it may provide important insight into serotonergic modulation of cortical networks.
SCZ Keywords 精神分裂症, schizophrenic
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