title: High frequency stimulation of afferent fibers generates asynchronous firing in the downstream neurons in hippocampus through partial block of axonal conduction.
abstract: 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 200Hz 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.
authors.affiliation: Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China. Electronic address: fengzhouyan@139.com.
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Zheshan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Durand
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods*; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D007395:Interneurons; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D009475:Neurons, Afferent / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D000078702:Radiofrequency Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Asynchronous; Axonal block; High frequency stimulation; Hippocampal CA1 region; Unit spike