Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex
Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex
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DOI：
10.1093/cercor/bhh184
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发表时间：
2005-06-01
期刊：
影响因子：
3.7
通讯作者：
Sejnowski, TJ
中科院分区：
文献类型：
--
作者：
Houweling, AR;Bazhenov, M;Sejnowski, TJ
慢性孤立的新皮层在几天到几周的时间内发展成慢性过度兴奋和局灶性癫痫。这种创伤后癫痫发生模型的机制还不清楚。我们假设，记录在慢性孤立的新皮层自发爆发性放电的结果从稳态可塑性（一种机制，通常假设稳定神经元活动）诱导的低神经元活动后去传入。为了验证这一假设，我们构建了新皮层的计算机模型，该模型结合了基于生物学的稳态可塑性规则，该规则用于维持放电率。去传入后，稳态上调锥体细胞上的兴奋性突触，无论有或没有同时下调抑制性突触或上调的内在兴奋性，启动缓慢重复的爆发放电，非常类似的癫痫样爆发放电记录在慢性孤立的新皮层。这些爆发性放电持续几百ms，以1-3 cm/s传播，由大量（10-15 mV）细胞内去极化组成，顶部有少量动作电位。我们的研究结果支持稳态突触可塑性作为创伤后癫痫发生的一种新机制的作用。
Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in chronically isolated neocortex. These burst discharges lasted a few hundred ms, propagated at 1-3 cm/s and consisted of large (10-15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of post-traumatic epileptogenesis.