title: High frequency stimulation extends the refractory period and generates axonal block in the rat hippocampus.
abstract: BACKGROUND
  The therapeutic mechanisms of deep brain stimulations (DBS) are not fully understood. Axonal block induced by high frequency stimulation (HFS) has been suggested as one possible underlying mechanism of DBS.
  
  
  OBJECTIVE
  To investigate the mechanism of the generation of HFS-induced axonal block.
  
  
  METHODS
  High frequency pulse trains were applied to the fiber tracts of alveus and Schaffer collaterals in the hippocampal CA1 neurons in anaesthetized rats at 50, 100 and 200 Hz. The amplitude changes of antidromic-evoked population spikes (APS) were measured to determine the degree of axonal block. The amplitude ratio of paired-pulse evoked APS was used to assess the changes of refractory period.
  
  
  RESULTS
  There were two distinct recovery stages of axonal block following the termination of HFS. One frequency-dependent faster phase followed by another frequency-independent slower phase. Experiments with specially designed temporal patterns of stimulation showed that HFS produced an extension of the duration of axonal refractory period thereby causing a fast recovery phase of the axonal block. Thus, prolonged gaps inserted within HFS trains could eliminate the axonal block and induced large population spikes and even epileptiform activity in the upstream or downstream regions.
  
  
  CONCLUSIONS
  Extension of refractory period plays an important role on HFS induced axonal block. Stimulation pattern with properly designed pauses could be beneficial for different requirements of excitation or inhibition in DBS therapies.
authors.affiliation: Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, PR China. Electronic address: fengzhouyan@139.com.
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, PR China.
authors.forename: Zheshan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, PR China.
authors.forename: Jiayue
authors.initials: J
authors.lastname: Cao
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: D000818:Animals; D001369:Axons / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000502:physiology*
keywords: Axon block; Deep brain stimulation; Hippocampus; Refractory period; Temporal patterns of stimulation