| Deep brain stimulation(DBS)is an emerging treatment for brain disorders.It has a good prospect in the treatment of Parkinson's disease,epilepsy,depression and other diseases.In contrast to traditional drug therapy or surgical lesion therapy,DBS has the advantages of reversible minor side and rapid effects.Previous studies have suggested many possible mechanism hypotheses,including the hypotheses of high-frequency stimulation suppressing the neuron firing,the hypotheses of high-frequency stimulation exciting the neuron firing and the hypotheses of high-frequency stimulation modulating the neuronal firing pattern.However,the mechanisms of high-frequency stimulation(HFS)of DBS are unclear.Recent studies have suggested that there is a certain rhythm in the spontaneous firing of neurons.Therefore,one of the manifestations of HFS changing the neuronal firing partern might be the change in the firing rhythm of the neurons.HFS might produce therapeutic effects by eliminating pathological rhythms in neuronal firing.To test the hypothesis,the present study investigated whether axonal HFS of afferent fibers could alter firing rhythms of downstream neurons.HFS trains of 1-min 100 Hz were applied on the Schaffer collaterals of the hippocampal CA1 region in anaesthetized rats.Single unit spikes of interneurons and pyramidal neurons in the downstream region was analyzed.The relationship between the firing sequence of the neuron and the ? rhythm in LFP was evaluated by the phase-locking value of the neuron spike firing sequence and the 0 rhythm in LFP before,during,and after HFS.In addition,the rhythms of unit spikes in three periods were evaluated by power spectrum density(PSD)of the autocorrelograms of unit sequences.The rhythms of local field potentials(LFP)and firing rhythms in the high frequency range of neurons during HFS were also evaluated by PSD.The possible mechanism of axonal HFS inducing changes of the firing rhythm in downstream neurons is discussed.The main findings of the paper include the following three parts:(1)It was confirmed that high frequency stimulation could suppress the rhythmic firing of neurons.During baseline recordings,spontaneous ? rhythms were obvious in the firing sequences of two types of neurons and in the LFP of the stratum radiatum.There was a significant phase-locking relationship between them.However,the axonal HFS could signifi antly weaken the phase-locking relationship:compared to the spontaneous state in the baseline recording,the phase-locking values between the spikes of pyramidal cells and the o rhythms in stratum radiatum decreased significantly from 0.36±0.12 to 0.06±0.04(P<0.001,paired t-test,n?8);the phase-locking values of interneuron spikes were also decreased significantly from 0.27±0.08 to 0.09±0.05(P<0.01,paired t-test,n=8).At same time ?rhythms of unit spikes of two types of neurons and ? rhythms in LFP were all suppressed significantly during HFS:compared to the spontaneous state in the baseline recording,the average power of the ? rhythm was reduced from 1.29±0.65 to 0.11±0.07 in the PSD plot of the pyramidal neuron spike sequence(P<0.01,paired t-test,n=7);the average power of the? rhythm was reduced from 1.62±0.79 to 0.12±0.06 in the PSD plot of the interneuron spike sequence(P<0.001,paired t-test,n=7).These results indicate that axonal HFS could significantly supress the spontaneous ? rhythm firing of downstream neurons.(2)Proposed a possible mechanism that axonal HFS supressed the spontaneous ?rhythmic firing of downstream neurons:the double modulation effect of HFS on the ?rhythm in LFP and the neuronal spike firing.Results of Pearson's correlation analysis showed that 20-30%variation in the ? rhythms of neuronal firing could be explained by the changes of LFP ? rhythms.It suggests that the attenuation of neuronal ? rhythm firing could be modulated by the attenuation of ? rhythm in the LFP of S.rad.In addition,the high-frequency electrical stimulation pulse also directly modulated the release of two types of neurons,inducing their firing rhythms of stimulation frequency rhythm.Axonal HFS might prevent the conduction of rhythmic excitation in the afferent fibers,thereby indirectly suppressing the rhythmic firing of individual neuron by suppressing rhythmic signals in downstream LFP;while the high-frequency stimulation pulse also induced a new firing pattern of downstream neurons and partially replaced the spontaneous rhythmic firing pattern.(3)New methods and new indexes for evaluating the rhythmic firing of neurons were designed.The paper proposed to use the phase-locking value to evaluate the phase relationship between the neuronal spike and the LFP.The power spectrum was obtained from the autocorrelation result of the binary neuronal firing sequence,and the rhythmic intensity of the neuronal firing was evaluated by the cumulative area of the power spectrum in the corresponding frequency range(the average energy in the corresponding fi-equency range).This quantitative index of analysis of neuronal rhythmic firing could be used not only to analyze the firing rhythms of interneurons and pyramidal neurons in the hippocampal CA1 region,but also to analyze other neuronal firing rhythms.In conclusion,the paper results showed that axonal HFS can change the spontaneous ?rhythmic firing of the downstream neuron and provided a possible mechanism for this effect:inducing a new spontaneous firing pattern and suppressing the rhythm of the field potential.The findings provide new evidences to support the hypothesis that HFS can alter the firing rhythms of neurons and also provide new clues to extend the scope of application of DBS. |
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