High-frequency stimulation of afferent axons alters firing rhythms of downstream neurons

Abstract

J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c eThis is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/) 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 invivo 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.

Correlated Activity in the Degenerate Retina Inhibits Focal Response to Electrical Stimulation

“…Conversely, abnormal neural activity, including local field potential and synchronization between neurons, is commonly found in neurological diseases such as Parkinson’s disease and epilepsy in addition to retinal degeneration ( Lian et al, 2003 ; Rubchinsky et al, 2012 ; Wang et al, 2016 ). For therapeutic approaches, various types of electrical stimulation have been attempted, such as closed-loop systems for antiphase LFPs ( Sanabria et al, 2020 ) and high-frequency stimulation above 100 Hz ( Santaniello et al, 2015 ; Ma et al, 2019 ), to suppress aberrant activity in these neuropathological fields. As a breakthrough to overcome low-resolution vision in patients with RP, it may be promising to apply therapies developed in other neurological fields to retinal degeneration.…”

Dynamics of neuronal firing modulated by high-frequency electrical pulse stimulations at axons in rat hippocampus

“…The initial 30 s periods of 2 min HFS were not used to analyze unit spikes due to the interference of the stimulationevoked PS [27,30]. The firing rhythms of both types of neurons were examined using the following spectrum of auto-correlograms for binary sequences representing the spike firing of individual neurons [26,33,34]. Firstly, the auto-correlogram of each binary sequence was calculated and normalized by its mean value to eliminate the impact of firing rate.…”

“…DBS typically utilizes high-frequency stimulations (HFS) with a constant pulse frequency in a range of 90-200 Hz [22,23]. Studies have shown that HFS can increase the neuronal firing downstream of stimulation sites through axonal projections and modulate the neuronal firing patterns [24][25][26][27][28]. It has been reported that HFS can also increase the LRTCs in LFP oscillations that represent integrated activity of a population of neurons [29].…”