Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation

作者：Rosenbaum Robert^*; Zimnik Andrew; Zheng Fang; Turner Robert S; Alzheimer Christian; Doiron Brent; Rubin Jonathan E

来源：Neurobiology of Disease, 2014, 62: 86-99.

DOI：10.1016/j.nbd2013.09.006

• Parkinson's disease
• Deep brain stimulation
• Axonal failure
• Synaptic failure
• Short term depression
• Beta oscillations

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 SIN 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 beta oscillations and synchrony during DBS. Our results support the idea that short term depression is a therapeutic mechanism of SIN DBS that works as a functional lesion by decoupling the somatic spiking patterns of SIN neurons from spiking activity in basal ganglia output nuclei.

• 出版日期2014-2