Divide and conquer: functional segregation of synaptic inputs by astrocytic microdomains could alleviate paroxysmal activity following brain trauma.
Divide and conquer: functional segregation of synaptic inputs by astrocytic microdomains could alleviate paroxysmal activity following brain trauma.
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DOI：
10.1371/journal.pcbi.1002856
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发表时间：
2013
影响因子：
4.3
通讯作者：
Sejnowski TJ
中科院分区：
文献类型：
--
作者：
Volman V;Bazhenov M;Sejnowski TJ
创伤性脑损伤经常导致癫痫发作。在其他因素中，稳态突触可塑性(HSP)通过不平衡的突触伸缩来介导创伤后癫痫的发生，部分补偿了创伤引起的神经兴奋性的丧失。肿瘤坏死因子α在一定程度上是由肿瘤坏死因子α介导的，肿瘤坏死因子DNA是创伤后早期反应性星形胶质细胞对慢性神经元不活动的反应而局部释放的。在这一早期阶段，肿瘤坏死因子α很可能局限于其神经胶质来源；然而，神经胶质细胞介导的空间定位的热休克蛋白在创伤后癫痫发生中的作用仍然知之甚少。我们使用计算模型来研究创伤后早期集体神经活动的重组。创伤和突触伸缩将非同步尖峰放电转变为阵发性放电。突触传入星形胶质细胞微区的功能性分离可降低阵发性发作的发生率。因此，我们认为创伤引发的反应性胶质细胞增厚对神经活动既有有益的影响，也有有害的影响。稳态可塑性是指神经元和神经元电路在突触输入受到干扰的情况下，为了维持生理上相关的电活动而调整其特性的能力。突触输入通常在脑损伤后立即慢性减少，先前的研究表明，稳态突触可塑性有助于创伤网络向癫痫发作的动态转变，这种情况被称为创伤后癫痫。这种稳态可塑性是由神经胶质细胞介导的，神经胶质细胞在创伤后不久就会释放调节分子。在这项研究中，我们使用计算模型来研究创伤后早期胶质细胞介导的可塑性的机制和意义。我们发现星形胶质细胞(胶质细胞的一种亚型)对创伤后神经活动的重组既有有益的影响，也有有害的影响。这表明，在功能失调的神经元网络中，神经胶质-神经元信号的某些方面可以缓解向病理活动的动态转变。
Traumatic brain injury often leads to epileptic seizures. Among other factors, homeostatic synaptic plasticity (HSP) mediates posttraumatic epileptogenesis through unbalanced synaptic scaling, partially compensating for the trauma-incurred loss of neural excitability. HSP is mediated in part by tumor necrosis factor alpha (TNFα), which is released locally from reactive astrocytes early after trauma in response to chronic neuronal inactivity. During this early period, TNFα is likely to be constrained to its glial sources; however, the contribution of glia-mediated spatially localized HSP to post-traumatic epileptogenesis remains poorly understood. We used computational model to investigate the reorganization of collective neural activity early after trauma. Trauma and synaptic scaling transformed asynchronous spiking into paroxysmal discharges. The rate of paroxysms could be reduced by functional segregation of synaptic input into astrocytic microdomains. Thus, we propose that trauma-triggered reactive gliosis could exert both beneficial and deleterious effects on neural activity. Homeostatic plasticity refers to the ability of neurons and neuronal circuitry to adjust their properties in order to maintain physiologically relevant electrical activity notwithstanding perturbations in synaptic input. Synaptic input is often chronically reduced immediately following brain trauma, and previous studies had suggested that homeostatic synaptic plasticity can aid in the dynamical transition of the traumatized network toward epileptic seizures, a condition known as “post-traumatic epilepsy”. This form of homeostatic plasticity is mediated by glial cells which release regulatory molecules shortly after trauma. In this study we used computational modeling to investigate the mechanisms and the implications of glial mediated plasticity early after trauma. We show that astrocytes (a subtype of glial cells) exert both beneficial and deleterious effects on post-traumatic reorganization of neural activity. This suggests that, in the dysfunctional neuronal network, some aspects of glial-neuronal signaling could alleviate the dynamical transition to pathological activity.
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影响因子：
16.2
作者：
Kaneko, Megumi;Stellwagen, David;Stryker, Michael P.
通讯作者：
Stryker, Michael P.
影响因子：
3.7
作者：
Houweling, AR;Bazhenov, M;Sejnowski, TJ
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作者：
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