Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation.
Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation.
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DOI：
10.1016/j.nbd.2013.09.006
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发表时间：
2014-02
影响因子：
6.1
通讯作者：
Rubin JE
中科院分区：
文献类型：
--
作者：
Rosenbaum R;Zimnik A;Zheng F;Turner RS;Alzheimer C;Doiron B;Rubin JE
丘脑底核 (STN) 的高频深部脑刺激 (DBS) 是帕金森病广泛使用的治疗方法，但其对基底神经节回路神经活动的影响尚不完全清楚。 DBS 增加了 STN 传出神经的兴奋，同时将 STN 尖峰模式与 STN 突触目标的尖峰模式解耦。我们认为，最近的研究表明 DBS 期间 STN 预测中轴突和突触失败率增加，从而解决了这一明显的悖论。为了研究这一假设，我们结合体外和体内记录，得出 DBS 期间轴突和突触衰竭的计算模型。我们的模型表明，这些故障会引起短期抑制，从而抑制从 STN 到其突触目标的放电频率振荡、同步性和速率编码信息的突触传递。特别是，我们的计算模型再现了广泛报道的 DBS 期间帕金森 β 振荡和同步的抑制。我们的结果支持这样的观点，即短期抑郁症是 STN DBS 的一种治疗机制，它通过将 STN 神经元的体细胞尖峰模式与基底神经节输出核的尖峰活动解耦来发挥功能性损伤的作用。
High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for Parkinson's disease, but its effects on neural activity in basal ganglia circuits are not fully understood. DBS increases the excitation of STN efferents yet decouples STN spiking patterns from the spiking patterns of STN synaptic targets. We propose that this apparent paradox is resolved by recent studies showing an increased rate of axonal and synaptic failures in STN projections during DBS. To investigate this hypothesis, we combine in vitro and in vivo recordings to derive a computational model of axonal and synaptic failure during DBS. Our model shows that these failures induce a short term depression that suppresses the synaptic transfer of firing rate oscillations, synchrony and rate-coded information from STN to its synaptic targets. In particular, our computational model reproduces the widely reported suppression of parkinsonian β oscillations and synchrony during DBS. Our results support the idea that short term depression is a therapeutic mechanism of STN DBS that works as a functional lesion by decoupling the somatic spiking patterns of STN neurons from spiking activity in basal ganglia output nuclei.
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影响因子：
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作者：
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