Pentylenetetrazol-induced epileptiform activity affects basal synaptic transmission and short-term plasticity in monosynaptic connections.
Pentylenetetrazol-induced epileptiform activity affects basal synaptic transmission and short-term plasticity in monosynaptic connections.
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DOI：
10.1371/journal.pone.0056968
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ghirardi M
中科院分区：
文献类型：
--
作者：
Giachello CN;Premoselli F;Montarolo PG;Ghirardi M
在实验模型中，癫痫活动通常通过局部应用致癫痫药物（包括广泛用于脊椎动物和无脊椎动物神经元的戊四唑（PTZ））来诱导。尽管这种神经系统疾病的高患病率和广泛的研究，癫痫发生的细胞和分子机制仍然不清楚。在这项工作中，我们研究了戊四氮诱导的神经元的变化，在体外形成的单突触回路，作为一个简单的实验模型，调查癫痫样活动的影响基础释放和强直后增强（PTP），一种形式的短期可塑性。我们观察到一个显着增强的基础突触强度，动力学类似于先前描述的使用依赖性形式的可塑性，确定的变化估计的量子参数，如容易释放池和释放概率。此外，这些神经元表现出强烈的减少PTP的表达和衰减时间常数，这表明突触囊泡池的动态重组后，长期刺激突触传递的损害。为了解释这种不平衡，我们确定癫痫活动是否与突触蛋白的磷酸化水平有关，这是已知的调节突触可塑性。使用蛋白质印迹和免疫细胞化学染色，我们发现PTZ依赖性增加突触蛋白磷酸化在PKA/CaMKI/IV和MAPK/ERK网站，这两个都是重要的调节突触可塑性。两者合计，我们的研究结果表明，延长癫痫样活动导致突触蛋白磷酸化状态的增加，从而有助于改变突触强度在基础条件和破伤风诱导的增强。
Epileptic activity is generally induced in experimental models by local application of epileptogenic drugs, including pentylenetetrazol (PTZ), widely used on both vertebrate and invertebrate neurons. Despite the high prevalence of this neurological disorder and the extensive research on it, the cellular and molecular mechanisms underlying epileptogenesis still remain unclear. In this work, we examined PTZ-induced neuronal changes in Helix monosynaptic circuits formed in vitro, as a simpler experimental model to investigate the effects of epileptiform activity on both basal release and post-tetanic potentiation (PTP), a form of short-term plasticity. We observed a significant enhancement of basal synaptic strength, with kinetics resembling those of previously described use-dependent forms of plasticity, determined by changes in estimated quantal parameters, such as the readily releasable pool and the release probability. Moreover, these neurons exhibited a strong reduction in PTP expression and in its decay time constant, suggesting an impairment in the dynamic reorganization of synaptic vesicle pools following prolonged stimulation of synaptic transmission. In order to explain this imbalance, we determined whether epileptic activity is related to the phosphorylation level of synapsin, which is known to modulate synaptic plasticity. Using western blot and immunocytochemical staining we found a PTZ-dependent increase in synapsin phosphorylation at both PKA/CaMKI/IV and MAPK/Erk sites, both of which are important for modulating synaptic plasticity. Taken together, our findings suggest that prolonged epileptiform activity leads to an increase in the synapsin phosphorylation status, thereby contributing to an alteration of synaptic strength in both basal condition and tetanus-induced potentiation.
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影响因子：
5.5
作者：
Debanne, D;Guerineau, NC;Thompson, SM
通讯作者：
Thompson, SM
影响因子：
2.9
作者：
ALTRUP, U
通讯作者：
ALTRUP, U
DOI：
10.1016/0742-8413(91)90290-a
发表时间：
1991-01-01
期刊：
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY
影响因子：
--
作者：
ALTRUP, U;LEHMENKUHLER, A;SPECKMANN, EJ
通讯作者：
SPECKMANN, EJ
影响因子：
5
作者：
BOULTON, CL;MCCROHAN, CR;OSHAUGHNESSY, CT
通讯作者：
OSHAUGHNESSY, CT
影响因子：
4.2
作者：
Casadio, A;Fiumara, F;Ghirardi, M
通讯作者：
Ghirardi, M