Development of neuronal activity and activity-dependent expression of brain-derived neurotrophic factor mRNA in organotypic cultures of rat visual cortex
Development of neuronal activity and activity-dependent expression of brain-derived neurotrophic factor mRNA in organotypic cultures of rat visual cortex
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DOI：
10.1093/cercor/9.8.864
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发表时间：
1999-12-01
期刊：
影响因子：
3.7
通讯作者：
Wahle, P
中科院分区：
文献类型：
--
作者：
Gorba, T;Klostermann, O;Wahle, P
我们分析了在器官型大鼠视觉皮层培养物中，脑源性神经营养因子（BDNF） mRNA的表达依赖于突触产生的自发生物电活性（SBA）的方式，并通过锥体细胞的记录进行监测。SEA起初很低，但从第四周开始，83%的神经元以0.2-1.2脉冲/秒的速度发射动作电位，处于兴奋和抑制的良好平衡状态。在第二周，BDNF mRNA的表达增加到与体内成人视觉皮层惊人的相似水平，尽管体外的活动率比体内报道的低10倍。因此，在没有感觉输入的情况下，由皮质神经元网络产生的SEA足以引发和维持BDNF的表达。在体外实验中，眼开眼后BDNF的短暂峰值没有出现。阻断SEA似乎不会改变神经营养因子(NT)-3和-4/5以及酪氨酸激酶受体C和B mRNA的表达。然而，BDNF的表达仍然极低。阻断一段时间后，SEA恢复，同时伴有短暂的高兴奋性。在钙通过电压门控通道与NMDA受体协同作用下，BDNF立即增加。核上层神经元的表达瞬间达到高水平。小核内神经元虽然激发动作电位，但恢复BDNF表达的速度要慢得多。体外恢复5天后，神经网络重新建立了兴奋和抑制的平衡状态。BDNF mRNA的分布和表达水平已恢复到中央水平。即使在“成人”培养中，SEA的急性阻断也会下调BDNF，随后SEA的恢复也会恢复BDNF的表达。我们认为，BDNF mRNA的表达依赖于SEA的变化，并对SEA的变化有快速的响应。稳态水平不依赖于活动的绝对水平，而更可能取决于兴奋和抑制之间的平衡，这表明BDNF在活动稳态中起作用。
We have analyzed in organotypic rat visual cortex cultures the way in which expression of brain-derived neurotrophic factor (BDNF) mRNA depends on synaptically generated spontaneous bioelectric activity (SBA) as monitored by recordings of pyramidal cells. SEA was initially low, but from the fourth week onwards 83% of the neurons fired action potentials at 0.2-1.2 impulses/s in a well-balanced state of excitation and inhibition. BDNF mRNA expression increased during the second week to a level surprisingly similar to the adult visual cortex in vivo, despite the fact that activity rates in vitro were similar to 10-fold lower than rates reported in vivo. Thus, SEA generated by a cortical neuronal network in the absence of sensory input is sufficient to elicit and maintain BDNF expression. The transient BDNF peak occurring after eye opening in vivo did not occur in vitro. A blockade of SEA seems not to alter the expression of neurotrophin (NT)-3 and -4/5, and tyrosine kinase receptor C and B mRNA. However, BDNF expression remained extremely low. A recovery of SEA after a period of blockade concurred with a transient hyperexcitability. BDNF immediately increased, driven by calcium influx through voltage-gated channels in synergy with NMDA receptors. Expression transiently reached high levels in neurons of supragranular layers. Infragranular neurons, although firing action potentials, recovered BDNF expression much slower. After 5 days in vitro recovery, the network had de novo established a balanced state of excitation and inhibition. Distribution and expression level of BDNF mRNA had returned to central. Even in 'adult' cultures an acute blockade of SEA downregulated BDNF, and a subsequent recovery of SEA restored BDNF expression. We conclude that BDNF mRNA expression depends on and responds with a fast kinetic to changes of the SEA. Steady-state levels do not depend on the absolute levels of activity, but more likely on the balance between excitation and inhibition, suggesting a role for BDNF in activity homeostasis.