噪声及水杨酸钠引起下丘及皮层的电活动改变
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摘要
背景
耳鸣为无相应的外界声源或电刺激，而主观存在的声音感觉。耳鸣的发生率约为3%-30%，约有l%-3%的人群因耳鸣而影响正常生活和工作。一些能导致听力损失(噪声暴露、老龄化、药物、外伤)的原因均可能引起神经性耳鸣。排除一些器质性病变而引起的耳鸣外，常见的神经性耳鸣多为主观性的。由于神经性耳鸣的客观评定方法局限，定位诊断困难，为临床治疗难题。
耳鸣的发生机制尚不清楚，一般认为，中枢听觉系统(CAS)的抑制性神经作用减弱，引起中枢神经电活动改变是耳鸣形成的神经生理基础。中枢听觉系统神经电活动改变可能是源于耳蜗损伤，引起包括听觉皮层(AC)、下丘(IC)和耳蜗核(CN)等中枢听觉系统，某些区域的抑制功能下调。耳鸣机制的研究应建立可靠的耳鸣动物模型,采用行为学或电生理学方法，结合耳鸣的临床特征进行研究。
本文利用噪声暴露和大剂量水杨酸钠（SS）建立动物模型，采用电生理学方法记录、分析和量化，对下丘和听觉皮层的改变进行分类和评估。
方法与结果
第一部分
用C57小鼠作为噪声暴露模型，16导微电极记录噪声暴露前后下丘神经的神经电活动反应情况。放电活动结果包括频率反应域和放电频率-声音强度函数，频率反应域结果表明某些下丘神经的特征性频率(CF)在噪声暴露前后由高频区域转变到低频区域，某些神经的最小阈值在噪声暴露后升高；而某些神经的最佳频率和最小阈值有明显升高；某些神经没有发生明显改变。放电频率-声音强度函数表明某些低频神经在噪声暴露后放电频率会增加，而高频神经在噪声暴露后放电频率会降低。比较噪声暴露前后的Q10值，在噪声暴露后调谐曲线的形状变宽，所记录的下丘神经自发性放电活动比暴露前减弱。
第二部分
（1）用成年Sprague Dawley（SD）大鼠作为动物模型，16导微电极记录大剂量SS注射前后听觉皮层神经的放电活动变化。腹部注射大剂量SS后3小时内听觉皮层放电活动递增。
（2）用成年SD大鼠,16导微电极记录,分别研究药物GABA类似物和钾离子通道开放剂对大剂量SS引起的听觉皮层高放电活动所产生的影响。分别测试了GABA类似物组、GABA类似物+SS组、钾离子通道开放剂组、钾离子通道开放剂+SS组。药物注射5分钟后注射水杨酸钠，GABA类似物+SS组和钾离子通道开放剂+SS组的放电率增加的幅度会低于水杨酸钠注射组。这表明GABA类似物和钾离子通道开放剂可部分抑制水杨酸钠引起的听觉皮层高放电活动。
结论
（1）噪声暴露可能引起下丘中枢侧抑制的损伤，这些抑制性区域一般存在于比下丘神经的特征性频率（CF）较低的频率区域，CF迁移和调谐曲线变宽主要发生在高于噪声暴露频率的神经区域，噪声暴露后下丘神经自发性放电即刻降低，这不同于噪声暴露一段时间后自发性放电的改变。上述电活动改变表明噪声暴露后耳蜗接受到的传入神经信号减少，影响正常的听觉传导通路，下丘神经的可塑性变化可能是引起耳鸣的原因，并解释了噪声引起的耳鸣频率范围与噪声的频率有关，即耳鸣的频率常低于噪声暴露频率。
（2）大剂量水杨酸钠可以引起听觉皮层放电频率增高，GABA类似物和钾离子通道开放剂可以降低听觉皮层的放电频率，这两种药物对大剂量水杨酸钠对听觉皮层的电生理功能均有影响。GABA类似物和钾离子通道开放剂可能对耳鸣有抑制作用。
上述研究会帮助我们进一步认识耳鸣的发生机制，对于耳鸣治疗也提供了线索。
Introduction
Tinnitus is the subjective sound sensation without corresponding external sound source orelectrical stimulation. The incidence of tinnitus is about3%-30%, about l%-3%of the everydaylife and work are affected by tinnitus. The causes of hearing loss (noise exposure, aging, drugs,trauma) are likely to induce tinnitus. Exclusion of tinnitus caused by organic disease, most oftinnitus are subjective. Due to the limit objective evaluation method of the neurogenic tinnitus,the diagnosis of localization of tinnitus is hard, it is a difficult problem for clinical treatment.
The mechanism of tinnitus is not clear. Generally, the inhibition of central auditory system(CAS) decreases, causing the electrical activity change of the CAS change is tinnitusneurophysiologic basis. Neural electrical activity change of the CAS may be due to cochleardamage, it is regarded that the cochlear damage can down regulate the inhibition of some areascentral auditory system (CAS) which include auditory cortex (AC), inferior cochlear(IC) andcochlear nucleus (CN).The study on tinnitus mechanism should depend on reliable tinnitusanimal models, behavioral or electrophysiological methods, combined with the characteristics oftinnitus clinic.
In this paper, we establish the animal model depending on noise exposure and high doses ofsodium salicylate (SS), the use of the electrophysiological methods to record, analyze andquantify, classify and assess changes in IC and AC.
Method and result
The first part, we use C57mice as noise exposure animal models. We use16channelmicroelectrode to get the response of IC neurons before and after the noise exposure. Thedischarge activity results include Frequency Response Area (FRA) and Rate Level Function(RLF). FRA results indicate the Characteristic Frequency (CF) of some of the IC neurons shiftfrom the high frequency area to the low frequency area after the noise exposure, the minimal threshold (MT) of some neurons is higher after the noise exposure. The BF and MT of some ofthe neurons change significantly after the noise exposure, however, BF and MT of some of theneurons do not change obviously. The RLF results show the spiking of the firing rate of eachneuron, only some of low frequency neurons show the higher firing rate after the noise exposure,however, higher frequency neurons show the lower firing rate of higher after the noise exposure.Compare the Q10value of the neurons before and after the noise exposure, it is indicated thatthe shape of the tuning curve became wider after the noise exposure, and the spontaneousactivity of each recorded neuron seems smaller than before.
The second part (1) We use Sprague Dawley(SD) rats as the animal models, the16channel microelectrode is used to record the electrical activity change of AC before and afterhigh doses of SS injection. The SS can induce AC response enhancement after the intraperitonealinjection in3hours.(2) We use SD rats and microelectrode is used to record, we study on theeffect of GABA analogue and potassium channel openers. We test the spiking of the firing rateof GABAB analogue group, GABA analogue+SS group, potassium channel opener group,potassium channel opener+SS group. After the drugs injection5minutes, we injected salicylate.The response of the firing rate of GABA analogue+SS group and GABA analogue+SS groupare increased less than that in salicylate injection group. It is indicated that GABA analogue andpotassium channel opener partially suppressed SS-induced hyperactivity in AC.
Conclusion
(1) Noise exposure may induce damage of the side-band inhibition in the IC, theseinhibition areas in lower frequency neurons than CF of IC. CF shifts and tuning curve wider ismainly found in higher frequency neurons than noise exposure frequency. The spontaneousactivity of IC neurons is decreased at once after the noise exposure, which is different from thespontaneous activity change after a period of noise exposure. The electrical activity changeabove indicates that cochlear receives afferent signals less after noise exposure, which affect theauditory pathway, The IC plasticity change may be the cause of the tinnitus, and explains thefrequency of the noise-induced tinnitus frequency range is related to the frequency of the noiseexposure, that is, the frequency of tinnitus is often lower than that of noise exposure.
(2) High doses of SS can induce the firing rate increasing, GABA analogues andpotassium channel openers can reduce the firing rate of the AC, these two drugs on affect the electrophysiological function of high doses of SS on the auditory cortex. GABA analogues andpotassium channel openers might inhibit tinnitus.
耳鸣为无相应的外界声源或电刺激，而主观存在的声音感觉。耳鸣的发生率约为3%-30%，约有l%-3%的人群因耳鸣而影响正常生活和工作。一些能导致听力损失(噪声暴露、老龄化、药物、外伤)的原因均可能引起神经性耳鸣。排除一些器质性病变而引起的耳鸣外，常见的神经性耳鸣多为主观性的。由于神经性耳鸣的客观评定方法局限，定位诊断困难，为临床治疗难题。
耳鸣的发生机制尚不清楚，一般认为，中枢听觉系统(CAS)的抑制性神经作用减弱，引起中枢神经电活动改变是耳鸣形成的神经生理基础。中枢听觉系统神经电活动改变可能是源于耳蜗损伤，引起包括听觉皮层(AC)、下丘(IC)和耳蜗核(CN)等中枢听觉系统，某些区域的抑制功能下调。耳鸣机制的研究应建立可靠的耳鸣动物模型,采用行为学或电生理学方法，结合耳鸣的临床特征进行研究。
本文利用噪声暴露和大剂量水杨酸钠（SS）建立动物模型，采用电生理学方法记录、分析和量化，对下丘和听觉皮层的改变进行分类和评估。
方法与结果
第一部分
用C57小鼠作为噪声暴露模型，16导微电极记录噪声暴露前后下丘神经的神经电活动反应情况。放电活动结果包括频率反应域和放电频率-声音强度函数，频率反应域结果表明某些下丘神经的特征性频率(CF)在噪声暴露前后由高频区域转变到低频区域，某些神经的最小阈值在噪声暴露后升高；而某些神经的最佳频率和最小阈值有明显升高；某些神经没有发生明显改变。放电频率-声音强度函数表明某些低频神经在噪声暴露后放电频率会增加，而高频神经在噪声暴露后放电频率会降低。比较噪声暴露前后的Q10值，在噪声暴露后调谐曲线的形状变宽，所记录的下丘神经自发性放电活动比暴露前减弱。
第二部分
（1）用成年Sprague Dawley（SD）大鼠作为动物模型，16导微电极记录大剂量SS注射前后听觉皮层神经的放电活动变化。腹部注射大剂量SS后3小时内听觉皮层放电活动递增。
（2）用成年SD大鼠,16导微电极记录,分别研究药物GABA类似物和钾离子通道开放剂对大剂量SS引起的听觉皮层高放电活动所产生的影响。分别测试了GABA类似物组、GABA类似物+SS组、钾离子通道开放剂组、钾离子通道开放剂+SS组。药物注射5分钟后注射水杨酸钠，GABA类似物+SS组和钾离子通道开放剂+SS组的放电率增加的幅度会低于水杨酸钠注射组。这表明GABA类似物和钾离子通道开放剂可部分抑制水杨酸钠引起的听觉皮层高放电活动。
结论
（1）噪声暴露可能引起下丘中枢侧抑制的损伤，这些抑制性区域一般存在于比下丘神经的特征性频率（CF）较低的频率区域，CF迁移和调谐曲线变宽主要发生在高于噪声暴露频率的神经区域，噪声暴露后下丘神经自发性放电即刻降低，这不同于噪声暴露一段时间后自发性放电的改变。上述电活动改变表明噪声暴露后耳蜗接受到的传入神经信号减少，影响正常的听觉传导通路，下丘神经的可塑性变化可能是引起耳鸣的原因，并解释了噪声引起的耳鸣频率范围与噪声的频率有关，即耳鸣的频率常低于噪声暴露频率。
（2）大剂量水杨酸钠可以引起听觉皮层放电频率增高，GABA类似物和钾离子通道开放剂可以降低听觉皮层的放电频率，这两种药物对大剂量水杨酸钠对听觉皮层的电生理功能均有影响。GABA类似物和钾离子通道开放剂可能对耳鸣有抑制作用。
上述研究会帮助我们进一步认识耳鸣的发生机制，对于耳鸣治疗也提供了线索。
Introduction
Tinnitus is the subjective sound sensation without corresponding external sound source orelectrical stimulation. The incidence of tinnitus is about3%-30%, about l%-3%of the everydaylife and work are affected by tinnitus. The causes of hearing loss (noise exposure, aging, drugs,trauma) are likely to induce tinnitus. Exclusion of tinnitus caused by organic disease, most oftinnitus are subjective. Due to the limit objective evaluation method of the neurogenic tinnitus,the diagnosis of localization of tinnitus is hard, it is a difficult problem for clinical treatment.
The mechanism of tinnitus is not clear. Generally, the inhibition of central auditory system(CAS) decreases, causing the electrical activity change of the CAS change is tinnitusneurophysiologic basis. Neural electrical activity change of the CAS may be due to cochleardamage, it is regarded that the cochlear damage can down regulate the inhibition of some areascentral auditory system (CAS) which include auditory cortex (AC), inferior cochlear(IC) andcochlear nucleus (CN).The study on tinnitus mechanism should depend on reliable tinnitusanimal models, behavioral or electrophysiological methods, combined with the characteristics oftinnitus clinic.
In this paper, we establish the animal model depending on noise exposure and high doses ofsodium salicylate (SS), the use of the electrophysiological methods to record, analyze andquantify, classify and assess changes in IC and AC.
Method and result
The first part, we use C57mice as noise exposure animal models. We use16channelmicroelectrode to get the response of IC neurons before and after the noise exposure. Thedischarge activity results include Frequency Response Area (FRA) and Rate Level Function(RLF). FRA results indicate the Characteristic Frequency (CF) of some of the IC neurons shiftfrom the high frequency area to the low frequency area after the noise exposure, the minimal threshold (MT) of some neurons is higher after the noise exposure. The BF and MT of some ofthe neurons change significantly after the noise exposure, however, BF and MT of some of theneurons do not change obviously. The RLF results show the spiking of the firing rate of eachneuron, only some of low frequency neurons show the higher firing rate after the noise exposure,however, higher frequency neurons show the lower firing rate of higher after the noise exposure.Compare the Q10value of the neurons before and after the noise exposure, it is indicated thatthe shape of the tuning curve became wider after the noise exposure, and the spontaneousactivity of each recorded neuron seems smaller than before.
The second part (1) We use Sprague Dawley(SD) rats as the animal models, the16channel microelectrode is used to record the electrical activity change of AC before and afterhigh doses of SS injection. The SS can induce AC response enhancement after the intraperitonealinjection in3hours.(2) We use SD rats and microelectrode is used to record, we study on theeffect of GABA analogue and potassium channel openers. We test the spiking of the firing rateof GABAB analogue group, GABA analogue+SS group, potassium channel opener group,potassium channel opener+SS group. After the drugs injection5minutes, we injected salicylate.The response of the firing rate of GABA analogue+SS group and GABA analogue+SS groupare increased less than that in salicylate injection group. It is indicated that GABA analogue andpotassium channel opener partially suppressed SS-induced hyperactivity in AC.
Conclusion
(1) Noise exposure may induce damage of the side-band inhibition in the IC, theseinhibition areas in lower frequency neurons than CF of IC. CF shifts and tuning curve wider ismainly found in higher frequency neurons than noise exposure frequency. The spontaneousactivity of IC neurons is decreased at once after the noise exposure, which is different from thespontaneous activity change after a period of noise exposure. The electrical activity changeabove indicates that cochlear receives afferent signals less after noise exposure, which affect theauditory pathway, The IC plasticity change may be the cause of the tinnitus, and explains thefrequency of the noise-induced tinnitus frequency range is related to the frequency of the noiseexposure, that is, the frequency of tinnitus is often lower than that of noise exposure.
(2) High doses of SS can induce the firing rate increasing, GABA analogues andpotassium channel openers can reduce the firing rate of the AC, these two drugs on affect the electrophysiological function of high doses of SS on the auditory cortex. GABA analogues andpotassium channel openers might inhibit tinnitus.
引文
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