High frequency stimulation of afferent fibers generates asynchronous firing in the downstream neurons in hippocampus through partial block of axonal conduction
High frequency stimulation of afferent fibers generates asynchronous firing in the downstream neurons in hippocampus through partial block of axonal conduction
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DOI：
10.1016/j.brainres.2017.02.008
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发表时间：
2017-04-15
期刊：
影响因子：
2.9
通讯作者：
Durand, Dominique M.
中科院分区：
文献类型：
--
作者：
Feng, Zhouyan;Wang, Zhaoxiang;Durand, Dominique M.
脑深部电刺激（DBS）是临床上治疗神经系统疾病的有效方法。然而，高频刺激（HFS）治疗DBS的机制尚未阐明。以往的研究表明，HFS引起的轴突传导的变化可能有重要的贡献DBS的影响，并需要进一步的研究。为了研究传入轴突的长时间HFS对下游神经元放电的影响，将100和200 Hz的HFS列车施加在麻醉大鼠海马CA1区的Schaffer侧支上。假设的锥体细胞和中间神经元在下游区域的单个单位活动进行了分析，在后期的延长HFS时，轴突传导被阻断。结果表明，在轴突阻滞期间，锥体细胞和中间神经元的放电频率不减反增。然而，放电率远小于HFS的刺激频率。此外，在HFS期间，锥体细胞的放电模式从基线记录期间的典型爆发变为规则的单棘波。此外，与单脉冲引起的同步放电相比，HFS在下游神经元中产生异步放电。据推测，HFS诱导的轴突传导阻滞是不完全的。在部分阻断期间，单个轴突可以间歇性地独立恢复，并驱动下游神经元以异步模式放电。HFS的这种轴突机制为DBS如何通过靶区域中的HFS调制的异步放电来替代神经元活动的原始模式从而产生DBS的治疗效果提供了新的解释。(C)2017 Elsevier B.V.版权所有。
Deep brain stimulation (DBS) is effective for treating neurological disorders in clinic. However, the therapeutic mechanisms of high-frequency stimulation (HFS) of DBS have not yet been elucidated. Previous studies have suggested that HFS-induced changes in axon conduction could have important contributions to the DBS effects and desiderate further studies. To investigate the effects of prolonged HFS of afferent axons on the firing of downstream neurons, HFS trains of 100 and 200 Hz were applied on the Schaffer collaterals of the hippocampal CA1 region in anaesthetized rats. Single unit activity of putative pyramidal cells and interneurons in the downstream region was analyzed during the late periods of prolonged HFS when the axonal conduction was blocked. The results show that the firing rates of both pyramidal cells and interneurons increased rather than decreased during the period of axon block. However, the firing rates were far smaller than the stimulation frequency of HFS. In addition, the firing pattern of pyramidal cells changed from typical bursts during baseline recordings into regular single spikes during HFS periods. Furthermore, the HFS produced asynchronous firing in the downstream neurons in contrast to the synchronous firing induced by single pulses. Presumably, the HFS-induced block of axonal conduction was not complete. During the period of partial block, individual axons could recover intermittently and independently, and drive the downstream neurons to fire in an asynchronous pattern. This axonal mechanism of HFS provides a novel explanation for how DBS could replace an original pattern of neuronal activity by a HFS-modulated asynchronous firing in the target region thereby generating the therapeutic effects of DBS. (C) 2017 Elsevier B.V. All rights reserved.