BACKGROUND Deep brain stimulation (DBS) is a successful clinical therapy for a wide range of neurological disorders; however, the physiological mechanisms of DBS remain unresolved. While many different hypotheses currently exist, our analyses suggest that high frequency (∼100 Hz) stimulation-induced synaptic suppression represents the most basic concept that can be directly reconciled with experimental recordings of spiking activity in neurons that are being driven by DBS inputs. OBJECTIVE The goal of this project was to develop a simple model system to characterize the excitatory post-synaptic currents (EPSCs) and action potential signaling generated in a neuron that is strongly connected to pre-synaptic glutamatergic inputs that are being directly activated by DBS. METHODS We used the Tsodyks-Markram (TM) phenomenological synapse model to represent depressing, facilitating, and pseudo-linear synapses driven by DBS over a wide range of stimulation frequencies. The EPSCs were then used as inputs to a leaky integrate-and-fire neuron model and we measured the DBS-triggered post-synaptic spiking activity. RESULTS Synaptic suppression was a robust feature of high frequency stimulation, independent of the synapse type. As such, the TM equations were used to define alternative DBS pulsing strategies that maximized synaptic suppression with the minimum number of stimuli. CONCLUSIONS Synaptic suppression provides a biophysical explanation to the intermittent, but still time-locked, post-synaptic firing characteristics commonly seen in DBS experimental recordings. Therefore, network models attempting to analyze or predict the effects of DBS on neural activity patterns should integrate synaptic suppression into their simulations.

中文翻译：

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深部脑刺激诱导突触抑制的理论原理

背景深部脑刺激 (DBS) 是一种成功的临床治疗方法，可用于治疗多种神经系统疾病；然而，DBS 的生理机制仍未得到解决。虽然目前存在许多不同的假设，但我们的分析表明，高频（~100 Hz）刺激诱导的突触抑制代表了最基本的概念，可以直接与 DBS 输入驱动的神经元尖峰活动的实验记录相一致。目标该项目的目标是开发一个简单的模型系统来表征兴奋性突触后电流 (EPSC) 和神经元中产生的动作电位信号，该神经元与由 DBS 直接激活的突触前谷氨酸能输入密切相关。方法我们使用 Tsodyks-Markram (TM) 现象学突触模型来表示 DBS 在广泛的刺激频率范围内驱动的抑制性、促进性和伪线性突触。然后将 EPSC 用作泄漏整合和激发神经元模型的输入，我们测量了 DBS 触发的突触后尖峰活动。结果 突触抑制是高频刺激的一个强大特征，与突触类型无关。因此，TM 方程用于定义替代 DBS 脉冲策略，以最小数量的刺激最大化突触抑制。结论 突触抑制为 DBS 实验记录中常见的间歇性但仍具有时间锁定的突触后放电特征提供了生物物理学解释。所以，