大鼠视觉发育可塑性关键期终止前后视皮层AMPA受体电流的发育变化

目的为了探索视觉发育可塑性关键期终止机制,对可塑性关键期终止前后,正常大鼠视皮层α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(amino-3-hydroxy-5-methylisoxazole-4-propionicacid,AMPA)受体介导的兴奋性突触后电流进行了研究。方法采用脑片膜片钳全细胞记录技术,记录生后3~8周正常大鼠视皮层AMPA受体介导的兴奋性突触后电流。结果在大鼠视皮层II-IV层,95例神经元形成全细胞记录,其中记录到AMPA受体电流43例;生后3~8周,视皮层神经元的输入阻抗、静息膜电位差异无统计学意义;生后3~8周,AMPA受体电流的潜伏期、上升时间、下降时间及半波宽差异无统计学意义;生后3~6周AMPA受体电流的幅值随发育逐渐增加,6~8周幅值变化不显著。结论视觉发育可塑性关键期高峰到成年阶段,大鼠视皮层神经元被动膜学特性无明显变化;AM-PA受体电流幅值随发育逐渐增加,关键期终止时达顶峰;突触后AMPA受体的功能变化可能参与了视觉发育可塑性关键期的终止过程。     

单眼形觉剥夺大鼠视皮层α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体GluR2的表达及其变化对微小兴奋性突触后电流的影响

目的 观察单眼形觉剥夺大鼠视皮层中α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic add,AMPA)受体的表达变化及其对突触后电流mEPSCs的影响,为研究其在视觉发育可塑性中的作用及机制做准备.方法 实验研究.取14 d龄健康Wistar大鼠40只,随机分为2组(Ⅰ、Ⅱ),每组20只,再随机分成A、B两组,每组10只.对实验组(Ⅰ组)行单眼形觉剥夺,正常饲养1周后对Ⅰ A组及ⅡA组常规心脏灌注、固定、切取视皮层,对组织切片行免疫组织化学法显色,显微镜观察AMPA受体GluR2的表达情况并进行图像分析,同时对Ⅰ B组及ⅡB组应用脑片膜片钳全细胞记录技术,获得大鼠视皮层神经元的细胞内微电极记录,记录突触后电流mEPSCs的变化.结果 AMPA受体GluR2在正常发育组视皮层中的表达较单眼形觉剥夺组视皮层中的表达水平高,差异有统计学意义(P<0.01).脑片膜片钳记录结果显示:AMPA受体介导的初级视皮层2/3层的锥体神经元的微小突触后兴奋性电流(mEPSCs)幅值增高.结论 大鼠出生后视皮层AMPA受体GluR2的水平受视觉刺激而发生变化,且其变化影响微小突触后兴奋性电流,提示其对出生后大鼠的视觉发育有着重要的生理作用.     

视觉正常人简单图形视觉刺激的视皮层功能定位及定量研究

目的 利用功能磁共振成像的方法定位、定量研究视觉正常人简单图形视觉刺激时的视皮层反应模式,为视皮层假体的刺激位置和强度提供参考.方法 对3名视觉正常成年志愿者进行圆环形棋盘格视觉任务的功能磁共振成像实验,同一任务对每位志愿者重复3次,以SPM2脑功能专业分析软件包作后期处理,显示视皮层反应模式.结果 3名受试者均较好完成视觉任务,平均体素反应总数为5217.3±1110.6.反应最强点坐标 x值为(-4.3±8.7)mm,y值为(-83.3±3.7)mm,z值为(-4.0±4.7)mm.平均最大反应强度为15.99±1.58,最大反应脑区为双侧的Brodmann 18区即初级视皮层V2区.解剖上的舌回附近.结论 利用功能磁共振成像的方法可以定位、定量的研究视皮层反应模式,这些反应模式信息可以为视皮层假体的刺激位置、强度等参数提供参考.     

多焦视诱发电位地形图

目的阐明多焦视诱发电位成分是如何从多通道双极记录中得出和进行地形学分析的.并研究不同的视皮层记录位置对多焦视诱发电位的波形、潜伏期(ms)和振幅(mV)的影响.方法采用多通道罗兰电生理系统(Retiscan,Wiesbaden/Brandenburg,Germany)分别测量50位正常人双眼不同视野的多焦视诱发电位(visual evoked potential,VEP)(最大的离心率为30°).两眼分别给予刺激.伪随机改变的刺激由多通道罗兰系统产生.刺激图形由60个刺激扇形组成,每个扇形又含16个方格,8个白色方格(＞130 cd/m2)和8个黑色方格(＜2 cd/m2).各个刺激单元的刺激翻转由一个伪随机序列控制.电极放置参照双极枕叶电极放置法,同时从4个前-后矢状中线及4个水平连线(横贯枕叶视皮层)上的皮肤电极上记录视觉诱发电位波形.上述电极可以是正极或负极.结果在记录的枕叶皮层区,不同记录通道所记录的VEP显示了不同的平均峰潜伏期和振幅值.在矢状中线上记录到的mVEP,其最大振幅值小于水平线上的记录值.另外,刺激视网膜不同部位所诱发的电位在头皮的位置是不同的.结论双极枕叶电极在矢状中线上记录到的mVEP与视野地形图记录的有良好的相关性.双极记录位置负极在枕骨粗隆,而正极在枕骨粗隆矢状轴上2 cm或4cm或正极在枕骨粗隆水平左、右4 cm时,记录得到的VEP结果更具可比性.为了更准确地评估客观视野缺损,可进行上下1/2或者水平1/2的多焦VEP记录.     

电刺激兔视神经诱发皮层电位的实验研究

目的 探讨电刺激兔眼视神经诱发皮层电位的波形、所需电刺激阈值及其影响因素.方法 用同心圆铂金电极对正常和碘酸钠注射后不同时期的48只青紫兰兔的视神经进行不同参数的电刺激.采用视皮层硬膜外电极记录诱发电位波形,采用多元线性回归分析电刺激阈值的影响因素.结果 变性的视神经、高刺激频率以及在硬脑膜上刺激所需的阈电流强度和阈电荷密度大,而大电极和短脉冲所需的阚电流强度较大,阈电荷密度较小.所需的阈电流强度为30～325 μA,阈电荷密度为20～93 μC/cm2.结论 电刺激视神经诱发皮层电位所需的电刺激阈值受刺激部位、刺激频率、刺激电极大小、电刺激脉冲持续时间以及视神经病理状态的影响.     

视网膜假体的研究进展

目前视网膜假体是所有视觉假体中研究最成熟、最广泛的一种,其研究目标是帮助失明患者恢复有用视力,尤其针对因视网膜色素变性和年龄相关性黄斑变性等致视力丧失者.依电刺激部位不同,视网膜假体分为视网膜上假体和视网膜下假体.前者通过玻璃体手术将微电极植入并固定于视网膜上;后者通过巩膜途径或玻璃体途径将微电极置于视网膜神经上皮层和视网膜色素上皮层之间.近年来对视网膜上假体的阵列电极、刺激电流等进行了改进;对视网膜下假体的芯片、供能方式等做了改进.有望为不可逆盲者提供帮助.     

胆碱能神经元在闪光刺激增强大鼠初级视皮层可塑性中的作用

目的　研究胆碱能神经元及递质在大鼠初级视皮层可塑性中的作用。方法　３６只（３６眼）成年ＳＤ大鼠随机分为３组:对照组、激动剂组、阻断剂组,每组各１２只（１２眼）。各组大鼠麻醉、固定后在初级视皮层（Ｖ１区）植入记录电极和玻璃微电极、在额叶植入参考电极,术后第７、８、９天于固定时间行紫光闪光刺激１ｈ,第１０天行微量注射Ｍ受体激动剂卡巴胆碱和Ｍ受体阻断剂东莨菪碱,注射后在相同闪光刺激条件下给予一串高频刺激,记录各组高频刺激前后Ｖ１区的视觉诱发电位,分析各组视觉诱发电位的幅值和峰时值的变化。检测不同组别大鼠在强直性闪光刺激后初级视皮层中胆碱乙酰转移酶（ＣｈＡＴ）、胆碱酯酶（ＡｃｈＥ）活性,Ｗｅｓｔｅｒｎｂｌｏｔ检测不同组别大鼠初级视皮层ＣｈＡＴ含量。结果　对照组和激动剂组在接受强直性闪光刺激后视觉诱发电位幅值较之前有显著性升高（均为Ｐ＜０．０１）,且峰时值变短（均为Ｐ＜０.０１）,阻断剂组幅值和峰时值在刺激前后差异无统计学意义（均为Ｐ＞０．０５）。在强直性闪光刺激后,与对照组相比,激动剂组幅值升高（Ｐ＜０．０１）、峰时值变短（Ｐ＜０.０１）,阻断剂组幅值降低（Ｐ＜０．０１）、峰时值变长（Ｐ＜０．０１）。对不同组别大鼠进行强直性闪光刺激后发现,与对照组相比,激动剂组的ＣｈＡＴ活性明显升高（Ｐ＜０．０５）、ＡｃｈＥ活性降低（Ｐ＜０．０５）;而阻断剂组的ＣｈＡＴ活性明显降低（Ｐ＜０．０５）,ＡｃｈＥ活性升高（Ｐ＜０．０５）;阻断剂组与激动剂组ＣｈＡＴ、ＡｃｈＥ活性差异显著（均为Ｐ＜０．０５）。ＣｈＡＴ蛋白的表达经Ｗｅｓｔｅｒｎｂｌｏｔ分析发现,与对照组比较,激动剂组有显著性升高（Ｐ＜０．０５）,阻断剂组有显著性降低（Ｐ＜０．０５）,阻断剂与激动剂组差异显著（Ｐ＜０.０５）。结论　强直性闪光刺激能使大鼠闪光视觉诱发电位呈现ＬＴＰ样反应,胆碱能神经元及递质系统参与了闪光刺激致大鼠初级视皮层的可塑性变化。     

发育对大鼠视皮层第2和3层锥体神经元AMPA受体介导的自发兴奋性突触后电流影响的研究

目的 研究发育过程中大鼠视皮层第2、3层锥体神经元的自发兴奋性突触后电流(sEPSC)变化,探讨生后早期自发性突触活动情况,以及视觉经验在视皮层发育过程中对神经元突触的修饰作用.方法 实验研究.应用红外微分干涉相差显微镜(IR-DIC)结合电耦合式摄像机(CCDCamera)可视法膜片钳全细胞记录生后2～7 d、8～14 d、15～21 d、22～28 d各组sEPSC变化,同时于电极内液中加入0.3%荧光黄对所记录细胞进行染色观察形态学改变.计量资料以均数±标准误表示,经方差齐性检验后,多组样本比较采用单因素方差分析,并进行样本均数间的多重比较.结果 4个组视皮层神经元sEPSC幅值分别为(14.13±0.73)、(15.01±0.62)、(19.87±0.75)、(22.09±1.14)pA,随发育逐渐升高(F=20.69,P＜0.01),但2～7 d组与8～14 d组差异无统计学意义(P＞0.05),而睁眼前8～14 d组较睁眼后15～21 d组幅值比较差异有统计学意义(P＜0.01).4个组视皮层神经元sEPSC频率分别为(1.35±0.05)、(1.33±0.12)、(2.26±0.15)、(2.85±0.12)Hz,随发育逐渐提高(F=87.46,P＜0.01),同样睁眼前8～14 d组较睁眼后15～21 d组频率比较差异有统计学意义(P＜0.01).视皮层第2、3层神经元胞体及突起以及生物电学特性随发育逐渐成熟.结论 视觉经验对于视皮层第2、3层神经元及突触发育成熟起了关键性作用.发育早期视皮层第2、3层有一定的α-氨基-3-羟基-5甲基-4-异号声(噁)唑丙酸(AMPA)受体功能表达,突触并非完全处于静息状态.     

小鼠视觉发育前关键期视皮层神经元反应特性与突触可塑性

背景 人类及哺乳动物的视觉发育主要是在生后关键期内完成的,但此期并非是哺乳动物接受视觉经验刺激的最早期.小鼠等哺乳动物视觉发育的关键期前还存在前关键期.目前,前关键期视皮层神经元的反应特性及突触可塑性研究仍处于探索阶段. 目的 探讨小鼠前关键期视皮层神经元的反应特性及突触可塑性特点. 方法 选择生后13～17 d的C57BL/6J小鼠48只,分别采用在体膜片钳全细胞记录及离体脑片膜片钳全细胞记录法记录小鼠视皮层第Ⅳ层神经元的电生理反应.在体记录在小鼠麻醉下进行,在电流钳模式下给予步阶电流刺激,测量其在体膜反应特性.给予最优刺激参数的移动光棒刺激,测量其视觉诱发反应特性.完成在体实验后行离体实验,分别测量神经元离体膜反应特性及白质-第Ⅳ层通路刺激条件下的诱发反应特性.采用随机数字表法将实验动物随机分成4个组,各组雌雄比例分配均匀.每组测定12个细胞,按照刺激频率的不同分别行低频刺激(LFS)和高频刺激[θ波脉冲刺激(TBS)]模式训练,按照刺激时序的不同进行突触前-后(pre-post)模式和突触后-前(post-pre)模式训练,在-70 mV电压钳制下分别记录训练前后兴奋性突触后电流(EPSCs).采用pClmap 10软件对原始数据进行预处理,采用Matlab 2008a软件进行统计分析.结果 在体成功记录的细胞数为39个,离体记录48个.在体和离体条件下视皮层第Ⅳ层神经元稳态平均发放动作电位(AP)个数分别为1.01±0.03和1.01±0.05,AP阈值分别为(-40.2±3.2)mV和(-39.6±2.0)mV,阈电流水平分别为(126.7± 17.4) pA和(129.6±17.5)pA,差异均无统计学意义(AP数:t=0.512,P=0.610;AP阈值:t=-1.074,P=0.286;阈电流:=-0.776,P=0.440).在体最优视觉刺激条件下平均膜电位峰值幅度为(7.3±4.3)mV,鲜见AP;离体最强通路刺激条件下平均膜电位峰值反应幅度为(6.4±2.8)mV,未见AP,在体与离体记录的平均膜电位峰值幅度差异无统计学意义(t=1.234,P=0.221).离体条件下,LFS训练前后EPSCs幅度分别为(138.1±51.9)pA和(76.1±34.8) pA,差异有统计学意义(t=4.437,P=0.001),而TBS训练前后EPSCs幅度差异无统计学意义(t=-0.756,P=0.466),pre-post训练前后EPSCs幅度分别为(122.4±62.2)pA和(78.5±46.7)pA,post-pre训练前后分别为(131.9±48.0)pA和(74.3±30.7)pA,差异均有统计学意义(pre-post:t=3.558,P=0.004;post-pre:t=4.283,P=0.001).结论 前关键期小鼠视皮层第Ⅳ层已完成神经回路的基本构建,但神经元的膜反应性以及突触连接仍未成熟.在低频或高频突触前后时序差异性输入条件下,突触功能受到抑制,而在高频输入条件下突触功能得到继续保持.前关键期小鼠视觉神经系统的发育具有不同于关键期的特征.     

培养鼠视皮层神经元γ-氨基丁酸激活电流的特点

目的:研究体外培养大鼠视皮层神经元GABA激活电流的特点.方法:用膜片钳记录仪采用全细胞模式记录体外培养大鼠视皮层神经元GABA激活电流.结果:大部分受检细胞可记录到明显去敏感的内向电流,且具有剂量依赖性.IGABA可被足量bicuculline完全阻断.GABAA受体的失敏恢复时间为5min.结论:体外培养视皮层神经元GABA激活电流的特点为探讨视觉形成及其发育机制提供了电生理学依据.     

Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development

PURPOSE: During the course of the development of visual prostheses, subretinal stimulation films were implanted in micropigs in order to prove the feasibility of subretinal electrical stimulation with subsequent cortical response. One aim was to demonstrate that epidural recording of visual evoked potentials is possible in the micropig. METHODS: Film-bound stimulation electrode arrays were placed in the subretinal space of micropigs. This enabled the retina to be stimulated subretinally. Since conventional visual evoked potential (VEP) measuring is virtually impossible in the pig from the neurosurgical point of view, epidural recording electrode arrays were positioned over the visual cortex as permanent electrodes. RESULTS: The feasibility of temporary implantation of film-bound stimulation electrode arrays was successfully demonstrated in the micropig model. On stimulation with monopolar voltage pulses (1000 to 3000 mV), reproducible epidural VEP measurements (5 to 10 micronV) were detected. CONCLUSIONS: The feasibility of subretinal stimulation of the retina was demonstrated in a retinal model that is similar to the human retina. This animal model therefore offers a suitable means of studying the tolerability of stimulation situations in the course of visual prosthesis development.     

Implantation and testing of subretinal film electrodes in domestic pigs

By definition, an electronic subretinal visual prosthesis requires the implantation of stimulation electrodes in the subretinal space of the eye. Polyimide film electrodes with flat contacts were implanted subretinally and used for electrical stimulation in acute experiments in anaesthetised domestic pigs. In two pigs, the film electrode was inserted through a sclerostomy into the vitreous cavity and, subsequently, via a retinotomy into the subretinal space around the posterior pole (ab interno approach). In three other pigs the sclera and pigment epithelium were opened for combined ab interno and transscleral positioning of the subretinal electrode. In all cases, perfluorocarbon liquid (PFCL) was used to establish a close contact between the film electrode and the outer retina. After cranial preparations of three pigs for epidural recording of visual cortex responses, retinal stimulation was performed in one pig with a film electrode implanted ab interno and in two pigs with film electrodes implanted by the ab interno and transscleral procedure. The five subretinal implantations were carried out successfully and each polyimide film electrode tip was positioned beneath the outer retina of the posterior pole. The retina was attached to the stimulation electrode in all cases. Epidural cortical responses to light and electrical stimulation were recorded in three experiments. Initial cortical responses to Ganzfeld light and to electrical stimuli occurred about 40 and 20 ms, respectively, after stimulation onset. The stimulation threshold was approximately 100 microA and, like the cortical response amplitudes, depended both on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. Our results in a domestic pig model demonstrate that polyimide film electrodes can be implanted subretinally and tested by recording cortical responses to electrical stimulation. These findings suggest that the domestic pig could be an appropriate animal model for basic testing of subretinal implants.     

Chronically implanted epidural electrodes in Göttinger minipigs allow function tests of epiretinal implants

Background To test the function of implantable devices for electrical stimulation of the retina, long-term registration tests of cortical-evoked potentials are required. Skin electrodes are not appropriate to provide representative recordings, due to the voluminous pneumatic frontal sinus of minipigs. Therefore, epidural electrodes were permanently implanted in minipigs and tested with visual and electrical retinal stimulation. The present study describes long-term recordings of electrically evoked cortical potentials in minipigs.Methods Three-channel silver-silver chloride electrodes were fixed on the epidura dorsal to the primary visual cortex of one hemisphere in Göttinger minipigs. Repeated light stimulation was performed and platinum-polyimide film multielectrode arrays were implanted on the retina for electrical stimulation and were later removed. Cortical potentials were recorded after stimulation with short biphasic charge-balanced currents.Results For up to 18 months, the implanted epidural electrodes allowed recording of visual cortex potentials evoked by visual or electrical retina stimulation. Small changes of response amplitudes in subsequent experiments indicated a stable location and recording properties of the cortex electrodes. Visual stimulation often yielded stronger responses for the contralateral eye. Superthreshold electrical retina stimulation evoked cortical responses with less delay compared to visual stimulation. We found threshold currents of 50 µA for charge-balanced biphasic trains of current impulses. Postoperative examination showed an attached and unchanged retina.Conclusions The minipig model is appropriate for the implantation of epiretinal stimulation electrodes and for the long-term tests of retinal implants by recording of cortical responses with chronically implanted epidural electrodes.This study was presented in part at the 100th annual meeting of the Deutsche Ophthalmologische Gesellschaft, 2002, Berlin.     

Penetrating electrode stimulation of the rabbit optic nerve: parameters and effects on evoked cortical potentials

Background

Stimulus parameters, in particular pulse shape, are an important consideration in the application of electrical stimulation when experimentally testing a visual prosthesis. We changed the biphasic pulse shape of several asymmetric charge-balanced pulses to investigate their effect on optic nerve (ON) stimulation and the recorded cortical response.

Methods

Monopolar platinum–iridium electrodes were implanted into the rabbit’s ON behind the eyeball. Electrical evoked potentials (EEPs) were recorded with silver ball electrodes placed on the cortex, and the results quantified.

Results

Our results indicate that changing the shape of cathodic-first charge-balanced biphasic pulse (CA) while maintaining charge balance could reduce the current thresholds for stimulation. When stimulated at the same charge density, the stimulus having high-amplitude short-duration (HASD) cathodic phase produced a higher amplitude response, with a larger spatial spread but with a lower current threshold compared with other stimuli. Adding an inter-phase gap between the two phases of the stimulus increased the EEP amplitude, but was saturated at a gap of ～0.2 ms; this was most obvious with CA stimulation, which was able to elicit a larger cortical response than that elicited by asymmetrical charge-balanced stimulus pulses with HASD cathodic phase, in contrast to CA without a gap. As the stimulating frequency increased, the amplitudes of the EEP components elicited by CA monotonically decreased. The fastest component (P0) was present with stimulating frequencies as high as 80 Hz, while the slower P1 and P2 disappeared with stimulating frequencies higher than 40 and 20 Hz, respectively.

Conclusion

A CA stimulus waveform with an inter-phase gap of 0.2 ms was more efficacious for ON stimulation than other stimulus combinations, and therefore should result in less tissue damage, minimal electrode etching, and lower power consumption if used in a visual prosthesis.     

Cortical potentials after electrical intraneural stimulation of the optic nerve during orbital enucleation

Background

The aim of this study was to present cortical potentials after electrical intraneural stimulation of the optic nerve during orbital enucleation due to malignant melanoma of the choroid or the ciliary body. These cortical potentials were related to cortical potentials after electrical epidural stimulation of the optic nerve, recorded during non-manipulative phases of neurosurgery for central skull base tumors.

Methods

Cortical potentials were recorded with surface occipital electrode (Oz) in six patients undergoing orbital enucleation under total intravenous anesthesia. Two thin needle stimulating electrodes were inserted inside the intraorbital part of the optic nerve. The electrical stimulus consisted of a rectangular current pulse of varying intensity (0.2?C10.0?mA) and duration (0.1?C0.3?ms); the stimulation rate was 2?Hz; the bandpass filter was 1?C1,000?Hz; the analysis time was 50?C300?ms.

Results

Cortical potentials could not be obtained or were inconsistently elicitable in three patients with longstanding history (>3?months) of severe visual deterioration, while they consisted of several positive and negative deflections in a patient with a short history of mild visual impairment. In two other patients, cortical potentials consisted of N20, P30 and N40 waves.

Discussion

Cortical potentials after electrical intraneural stimulation of the optic nerve could be recorded in patients with a short history of visual deterioration and without optic nerve atrophy and appear more heterogeneous than cortical potentials after electrical epidural stimulation of the optic nerve, recorded during non-manipulative phases of neurosurgery for central skull base tumors.     

扫描视觉诱发电位（SVEP）对成年野生型C57BL/6J小鼠客观视力评估的可靠性

目的　评价扫描视觉诱发电位（sweep visual evoked potential,SVEP）对成年野生型C57BL/6J小鼠客观视力评估的可靠性。方法　选取6只鼠龄32~33 d的正常野生型C57BL/6J小鼠,雌雄不限,麻醉小鼠将记录电极 （2 mm直径的钨电极） 放置在λ缝旁3 mm的左皮质（受刺激右眼的对侧）,深度为皮层下400 μm,额部的针状电极作为参考电极,尾部的针状电极作为接地电极,记录过程中遮盖左眼（未受刺激眼）,屏幕放置在小鼠眼前20 cm处,视野范围为100°（水平）×82°（垂直）,平均亮度为25 cd·m^-2;采用垂直方向的正弦波光栅刺激,刺激对比度为100%,包括11个空间频率,时间频率为1 Hz;整个扫描过程需要12 s（11 s空间频率+ 1 s预适应）,数据的误差值稳定后取其平均值。分别记录左右眼对应的视皮层VEP波形。不同刺激频率给予20次刺激,每眼重复测量3~4次,取其平均值,左右眼交替试验。以空间频率对数作为x轴,经离散傅里叶分析所得反应振幅为y轴建立坐标系,选取临近噪点的4个有效测定点行线性回归,回归曲线外推法至振幅为0处的空间频率即为推断的客观视力。结果　空间频率为0.05 c·deg^-1时,SVEP提示N100波振幅达到峰值。随着逐步增加刺激空间频率,SVEP振幅降低﹑潜伏期延迟,空间频率为0.65 c·deg^-1时视皮层电反应几乎无法与噪点区分;6只小鼠右眼空间频率视力为（0.56±0.04）c·deg^-1,左眼为（0.50±0.04）c·deg^-1,两眼空间频率视力比较差异无统计学意义（P>0.05）;12眼空间频率视力为（0.53±0.03）c·deg^-1。结论　可以使用SVEP评估小鼠客观视力,此方法与行为方法测得的视力相近,但SVEP评估小鼠视力结果更为客观精确,所需时间更短。     

Intraorbital optic nerve stimulation with penetrating electrodes: in vivo electrophysiology study in rabbits

Purpose  To investigate the response properties of the electrically evoked potentials (EEPs) elicited by intraorbital optic nerve stimulation with penetrating electrodes using different stimulus parameters. Methods  Visually evoked potentials (VEPs) were recorded as a control and for comparative purposes. Teflon-coated tungsten wire electrodes (100 μm core-diameter, 300 μm exposed tip) were inserted intraorbitally into the optic nerve. A charge-balanced biphasic current was delivered to the optic nerve via inserted wire electrodes in 26 anaesthetized rabbits. EEPs were recorded by epidural electrodes placed over the visual cortex. The charge density threshold for eliciting EEPs was determined. Stimulus pulse amplitude, duration, frequency and waveform were varied to study their effects on EEPs. After the experiments, the stimulated optic nerves were examined histologically for examination of implantation position of the stimulating electrode into the optic nerve tissue. Results  EEPs were successfully elicited by intraorbital optic nerve stimulation with penetrating electrodes. The measured amplitude of the first large positive peak (P1) was smaller and the latency of P1 was shorter compared with VEPs. The measured charge density threshold to elicit EEPs was 21.36 ± 5.64 μC/cm². The amplitude of P1 increased and the latency of P1 decreased with increasing pulse amplitude of fixed duration stimuli. The amplitude of P1 increased with increasing pulse duration of fixed amplitude stimuli. For fixed charge stimuli, the amplitude of P1 decreased and the latency of P1 increased as the pulse duration increased. As frequency of stimuli varied from 1 to 10 Hz, the amplitude of P1 decreased monotonically. Among the different charge-balanced biphasic pulse stimulating waveforms, the symmetrical cathode-first biphasic pulse elicited the largest amplitude of P1. Conclusions  Our study demonstrates that intraorbital optic nerve stimulation with different stimulus parameters by penetrating electrodes can evoke cortical responses with different properties. The short-duration symmetrical cathode-first biphasic pulses of current with low frequencies are more efficacious in eliciting electrophysiological responses in the visual cortex than other stimulating waveforms. This research is supported by the National Basic Research Program of China (973 Program, 2005CB724302), National Science Fund for Distinguished Young Scholars from The National Natural Science Foundation of China (60588101), Shanghai Pujiang Program (07pj14050), Shanghai Commission of Science and Technology (05DZ22318, 05DZ22325, 04DZ05114).     

Focal activation of the feline retina via a suprachoroidal electrode array

This paper presents the results of the first investigations into the use of bipolar electrical stimulation of the retina with a suprachoroidal vision prosthesis, and the effects of different electrode configurations on localization of responses on the primary visual cortex. Cats were implanted with electrodes in the suprachoroidal space, and electrically evoked potentials were recorded on the visual cortex. Responses were elicited to bipolar and monopolar stimuli, with each stimulating electrode coupled with either six-return electrodes, two-return electrodes, or a single-return electrode. The average charge threshold to elicit a response with bipolar stimulation and six-return electrodes was 76.47 ± 8.76 nC. Bipolar stimulation using six-return electrodes evoked responses half the magnitude of those elicited with a single or two-return electrodes. Monopolar stimulation evoked a greater magnitude, and area of cortical activation than bipolar stimulation. This study showed that suprachoroidal, bipolar stimulation can elicit localized activity in the primary visual cortex, with the extent of localization and magnitude of response dependent on the electrode configuration.