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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (1): 33-41    DOI: 10.31083/j.jin.2019.01.18
Original Research Previous articles | Next articles
High-frequency stimulation of afferent axons alters firing rhythms of downstream neurons
Weijian Ma1, Zhouyan Feng1, *(), Zhaoxiang Wang1, Wenjie Zhou1
1Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China
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Abstract  

Deep brain stimulation is an emerging treatment for brain disorders. However, the mechanisms of high-frequency brain stimulation are unclear. Recent studies have suggested that high-frequency stimulation might produce therapeutic effects by eliminating pathological rhythms in neuronal firing. To test the hypothesis, the present study investigated whether stimulation of axonal afferent fibers might alter firing rhythms of downstream neurons in in-vivo experiments with Sprague-Dawley rats. Stimulation trains of 100 Hz with one minute duration were applied to the Schaffer collaterals of hippocampus Area CA1 in anaesthetized rats. Spikes of single interneurons and pyramidal neurons in the downstream region were analyzed. The spike rhythms before, during, and after the stimulations were evaluated by analyzing the power spectrum density of autocorrelograms of the spiking sequences. The rhythms of local field potentials were also evaluated by power spectrum density. During baseline recordings, theta rhythms were obvious in the spiking sequences of both types of neuron and in the local field potentials of the stratum radiatum. However, these theta rhythms were all suppressed significantly during the stimulations. Additionally, the results of Pearson's correlation analysis showed that 20-30% variation in the theta rhythms of neuronal firing could be explained by changes of the theta rhythms in local field potentials. High-frequency axonal stimulation might prevent the original rhythmic excitation in afferent fibers and generate new excitation by stimulation pulses per se, thereby suppressing the theta rhythms of individual neuron firing and of local field potentials in the region downstream from stimulation. The results provide new evidence to support the hypothesis that high-frequency stimulation can alter the firing rhythms of neurons, which may underlie the therapeutic effects of deep brain stimulation.

Key words:  Deep brain stimulation      high frequency stimulation      unit spike      theta rhythm      local field potential      autocorrelogram      power spectrum density      axonal block      hippocampus area CA1     
Submitted:  23 January 2018      Accepted:  28 March 2019      Published:  30 March 2019     
Fund: 
  • 30970753/National Natural Science Foundation of China
  • 2018DG0ZX01/Major Scientific Project of Zhejiang Lab
*Corresponding Author(s):  Zhouyan Feng     E-mail:  fengzy@mail.bme.zju.edu.cn

Cite this article: 

Weijian Ma, Zhouyan Feng, Zhaoxiang Wang, Wenjie Zhou. High-frequency stimulation of afferent axons alters firing rhythms of downstream neurons. Journal of Integrative Neuroscience, 2019, 18(1): 33-41.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2019.01.18     OR     https://jin.imrpress.com/EN/Y2019/V18/I1/33

Figure 1.  Spontaneous theta rhythms of neuronal firing in hippocampus Area CA1 of anaesthetized rats. (A) Left: Schematic diagram of the rat hippocampus and electrode location. Recording electrode (RE) and stimulating electrode (SE) were respectively located in hippocampus Area CA1 and in the upstream Schaffer collaterals. Arrow indicates direction of stimulus-induced excitation. Electrical signals in the pyramidal layer (Pyr. layer) and in the stratum radiatum (S. rad.) were collected by two recording sites in the RE array (separated by 0.4 mm). Right: Typical waveforms of the population spike (PS) and field excitatory postsynaptic potential (fEPSP) evoked by a stimulus and recorded in Pyr. and S. rad. layers, respectively. Inverted triangles: Truncated stimulus artifacts. (B) Left: Segment of raw recording in the Pyr. layer together with associated local field potential (LFP) in theta range and multiple unit activity (MUA). Middle: Autocorrelation profile of the sequence of unit spikes extracted from the MUA. Right: Corresponding LFP-power spectrum density (top: LFP-PSD) and unit spike-power spectrum density (bottom: unit-PSD). (C) Left: Recording from S. rad. corresponding to the segment in (B) with its LFP in theta range. Right: Corresponding LFP-power spectrum density. Shaded area: Theta range (2-5 Hz).

Figure 2.  Changes in the multiple unit activity and local field potential evoked by stimulation (one minute, 100 Hz). (A) Example recording from Pyr. layer and associated multiple unit activity and local field potential in theta range. Typical spike waveforms of interneurons and pyramidal neurons are given in the two expanded insets. (B) Corresponding recording from S. rad. layer. Shaded area: High-frequency stimulation period, stimulus artifacts removed.

Figure 3.  Axonal stimulation suppressed theta rhythms in neuronal firing. (A) Top to bottom: Examples of theta signal recorded from Pyr. layer, raster plots of unit spikes of an interneuron and a pyramidal neuron, and theta signal from S. rad. during the three periods of: before, during, and after high-frequency stimulation, respectively. (B) Example autocorrelation profiles and their unit-power spectrum densities (unit-PSD) for interneuron spikes during the three different periods. (C) Statistical power of theta rhythms in unit-PSD of interneurons during the three different periods. Paired $t$-test was used to compare mean power during stimulation and baseline mean power prior to stimulation (** p < 0.01, $n$ = 7). (D) and (E) Corresponding data for pyramidal neurons.

Figure 4.  Axonal stimulation suppressed theta rhythms in the local field potential. (A) and (B) Examples of local field potential-power spectrum densities in Pyr. layer (A) and S. rad. (B) for the three different periods: before, during, and after stimulation. (C) and (D) Statistical comparison of the power of theta rhythms (2-5 Hz) for the three different periods. $^{*}$p < 0.05, $^{**}$p < 0.01, paired $t$-test, $n$ = 7.

Figure 5.  Correlation between theta rhythm of neuronal firing and theta rhythm of local field potential. Scatter diagrams of theta power of unit spikes (A and C for interneurons, B and D for pyramidal neurons) against the corresponding theta power of local field potential (A and B for Pyr. Layer, C and D for S. rad.). Pearson's correlation coefficient (R) is shown above each plot together with the p-value. The data number ($N$ = 3 $\times$ 7 = 21) is the number of pooled data from the three different periods of before, during, and after stimulation within the seven experiments.

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