高频脑深部电刺激对帕金森病模型大鼠丘脑底核神经元放电的影响

目的观察高频电刺激丘脑底核对帕金森病大鼠丘脑底核神经元放电的影响。方法应用6-羟基多巴胺制备偏侧帕金森病大鼠模型,在其丘脑底核区插入刺激电极进行高频电刺激,采用细胞外单位记录的方法记录刺激前和刺激过程中丘脑底核神经元的放电。结果电刺激前对照组和帕金森组丘脑底核神经元放电频率无显著差异,而放电形式不同,对照组大部分丘脑底核神经元表现为规则或不规则放电,帕金森组丘脑底核神经元以爆发放电为主;高频电刺激两组大鼠丘脑底核神经元后,两组丘脑底核神经元放电都主要表现为部分抑制或完全抑制。结论爆发式放电增多可能是帕金森发病潜在的电生理基础。高频电刺激丘脑底核可抑制丘脑底核的异常放电活动,这可能是脑深部电刺激治疗帕金森病的可能机制之一。     

丘脑底核电刺激对癫痫大鼠模型基底节神经元放电的影响

目的应用不同频率的电刺激海人酸模型癫痫大鼠STN核,观察STN核以及SNr(黑质网状部)神经元细胞在刺激后放电频率的变化,研究电刺激STN对STN内神经元和SNr神经元放电的影响,探讨STN-DBS治疗癫痫的作用机制。方法10只癫痫大鼠为实验组,另10只正常大鼠作为对照组。参照大鼠立体定向图谱,将记录的玻璃微电极和刺激电极分别插入STN、SNr核团内,刺激频率分为三组,分别为30 Hz、130 Hz、260 Hz。通过单神经元放电细胞外记录方法分别于高频刺激前后记录脑内核团神经元放电情况,分析神经元在STN-HFS刺激前和刺激时放电改变情况。结果正常大鼠的STN及SNr神经元放电与癫痫模型大鼠相比,两者放电频率不存在显著性差异,对放电模式的分析发现两者也无明显差异(P>0.05)。癫痫大鼠的STN及SNr神经元在30 Hz的刺激过程中放电频率多数没有明显变化。随着放电频率的增加两种神经元在电刺激后多数神经元放电明显受到抑制。在130 Hz和260 Hz组,受抑制的神经元较30 Hz组明显增加,具有显著性差异(P<0.05)。结论本研究证实高频电刺激STN明显抑制了STN和SNr神经元的兴奋性,其效果与频率是相...     

反复惊厥阈下痫样放电致大鼠持续性情绪唤醒障碍

目的 探讨反复惊厥阈下痫样放电是否可引发实验大鼠较长时间的情绪唤醒障碍.方法 选择6～7周龄雄性SD大鼠62只,成组设计,随机分为惊厥阈下痫样放电组(subelinical epileptifor mdis charges group,SED组,n=16)、海马快速电点燃组(hippoeampal kindling group,HK组,n=16)、海马电极埋植对照组(control of electrode group,EC组,n=15)、正常对照组(normal control group,NC组,n=15),建立大鼠反复SED动物模型,通过运动活性、探究行为、拒俘反应性、高架十字迷宫实验,观测电刺激停止后1、7和30 d时实验大鼠情绪唤醒水平改变.结果 与EC组相比,电刺激后7 d,HK组、SED组大鼠旷场爬越行为明显减少(P<0.01),后肢性站立、进入高架十字迷宫开臂次数百分比和滞留时间百分比降低(P<0.05),电刺激后30 d上述差异仍存在(P<0.05),同时,HK组、SED组大鼠拒俘反应性在电刺激后30 d有明显增加(P<0.01).结论 反复惊厥阈下痫样放电引起了实验大鼠持续性运动活性减少、探究行为受抑、警觉水平过高、焦虑不安状态、环境适应能力下降、惊恐逃避反应等多种情绪唤醒障碍.     

神经性厌食症大鼠伏隔核神经元局部场电位分析

目的观察神经性厌食症大鼠模型伏隔核神经元的电活动并分析其局部场电位。方法实验动物分为运动诱发的厌食症(activity-based anorexia,ABA)大鼠模型组及对照组(各12只)。ABA模型的建立基础是模型大鼠不受限制的滚轮运动以及限制饮食(1h/d),通过这种限制饮食及过度活动,造成明显的体重下降,从而模拟AN的行为学特征。通过微阵列电极记录大鼠在神经性厌食症病理及正常生理状态下伏隔核神经元的局部场电位。结果电生理记录显示模型组大鼠NAc神经元平均放电频率为(6.89±2.67)Hz,对照组为(3.22±1.23)Hz。模型组大鼠伏隔核神经元放电的峰峰间期散点图在200ms以下有密集分布。模型组伏隔核神经元放电峰峰间期直方图呈逐渐衰减的正偏态分布,对照组伏隔核神经元放电峰峰间期直方图呈对称分布;回归映射分析结果显示病理状态下数据明显较生理状态下集中。功率谱密度分析显示模型组在10~20Hz范围内出现了能量高值成分。结论神经性厌食症模型大鼠伏隔核神经元较生理状态下放电频率明显增加,峰峰间期序列发生明显变化,局部场电位模式发生变化。     

帕金森病大鼠苍白球神经元放电模式的分析

目的 探讨帕金森病(Parkinson's disease,PD)大鼠苍白球(globus pallidus,GP)神经元的放电模式,为研究帕金森病的病理生理过程提供实验依据.方法 大鼠30只,应用6-羟基多巴胺(6-hydroxydopamine,6-OHDA)建立PD大鼠模型(模型组),多种方法对模型进行评价.在立体定向仪引导下记录PD模型组及正常生理状态下大鼠(对照组,10只)GP神经元放电活动,并对其放电模式进行分析.结果 模型组大鼠中有13只行为学及病理学检测结果符合PD模型标准.电生理记录显示对照组大鼠GP神经元放电频率为6±2Hz,模型组大鼠GP神经元放电频率为21±3Hz,模型组大鼠的放电频率显著高于对照组(P＜0.05).对照组共记录到四种形式的放电模式,模型组记录到三种.对照组GP神经元簇发放电模式的比例为11%,而模型组GP神经元簇发放电模式的比例术后四周为59%,术后八周为61%,两者比较具有统计学意义(P＜0.05).结论 PD模型大鼠GP神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大.这可能在帕金森病的病理生理变化中具有重要作用.     

高频电刺激丘脑底核对黑质神经元保护作用的研究

目的探讨高频电刺激丘脑底核对帕金森病(PD)大鼠黑质致密部(SNc)神经元的保护作用及机制。方法将40只SD大鼠随机分为3组,正常对照组10只,模型组及刺激组各15只。模型组及刺激组大鼠于脑内侧前脑束注射6-羟基多巴胺(6-OHDA)制备大鼠偏侧PD模型,刺激组大鼠丘脑底核区植入刺激电极实施高频电刺激(130Hz),对三组动物的行为学、SNc神经元的形态学改变进行观察和分析。结果术后2、4周时,刺激组SNc神经元凋亡的阳性率分别为(39.98±12.11)%和(41.12±9.23)%,模型组则为(61.74±7.82)%和(67.12±10.23)%;两组比较,差异有统计学意义(P<0.05)。术后2、4周时,刺激组Bcl-2/Bax比值为0.84±1.01和0.88±0.81,模型组则为0.39±0.15和0.30±0.58;两组比较,差异有统计学意义(P<0.05)。结论高频刺激丘脑底核对PD大鼠黑质SNc神经元有保护作用,其机制可能与改变了SNc区神经递质的分布和代谢有关。     

高频电刺激丘脑底核对偏侧帕金森病猴模型苍白球内侧部神经元放电的影响

目的 探讨深部电刺激丘脑底核(STN)治疗帕金森病(PD)的可能作用机制. 方法 通过在模型猴单侧大脑注入1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备偏侧PD模型,随后在立体定向技术下参照猴脑立体定向图谱,将记录的玻璃微电极和刺激电极分别插入苍白球内侧部(Gpi)和STN内,通过单细胞胞外记录法记录并分析神经元刺激前和刺激时的放电改变情况. 结果 PD猴未注药侧GPi神经元自发放电较规则,放电频率为(44.38±13.66)锋电位/s;注药侧GPi神经元放电频率为(50.57±15.53)锋电位/s,较未注药侧稍快但差异无统计学意义(P＞0.05).刺激过程中GPi神经元存在4种反应:部分抑制、完全抑制、兴奋和无变化,多数神经元表现为受到抑制,注药侧更为明显,平均抑制率为56.29％±29.66％,高于未注药侧的36.03％±35.25％,差异有统计学意义(P＜0.05). 结论 深部电刺激术治疗PD的作用机制为通过高频刺激对STN神经元异常兴奋性的调控,改变相关的联系核团如GPi或黑质网状部(SNr)的异常功能状态,最终使基底节运动环路正常控制功能重新恢复,进而改善PD症状.     

神经性厌食症大鼠伏隔核神经元电活动及峰峰间期序列的分析

目的观察神经性厌食症大鼠模型伏隔核神经元的电活动并分析其峰峰间期。方法通过微阵列电极记录大鼠在神经性厌食症病理及正常生理状态下伏隔核神经元的自发放电活动。结果电生理记录显示模型组大鼠NAc神经元平均放电频率为6.89±2.67Hz,对照组大鼠NAc神经元平均放电频率为3.22±1.23Hz。(P=0.001)。模型组大鼠伏隔核神经元放电的峰峰间期散点图在200ms以下有密集分布。模型组伏隔核神经元放电峰峰间期直方图呈逐渐衰减的正偏态分布,对照组伏隔核神经元放电峰峰间期直方图呈对称分布。结论神经性厌食症模型大鼠伏隔核神经元较生理状态下放电频率明显增加,峰峰间期序列发生明显变化。     

ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛反应电活动的影响

目的研究ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛兴奋神经元(pain-excitation neurons,PEN)和痛抑制神经元(pain-inhibitationneurons,PIN)电活动的影响,进一步探讨ACh对正常和吗啡成瘾状态下CA1区痛觉调制的作用及机制。方法电刺激坐骨神经作为伤害性电刺激,在细胞外用玻璃微电极记录CA1区PEN和PIN的放电,观察ACh对正常大鼠和吗啡成瘾大鼠CA1区PEN和PIN电活动的影响。结果伤害性刺激能够增强PEN的电活动,而减弱PIN的电活动。正常大鼠中,ACh使PEN的痛诱发放电频率降低,PIN的放电频率增加;ACh的作用在注射后4 min达到峰值。吗啡成瘾大鼠中,ACh同样也抑制了PEN的电活动,兴奋PIN的电活动,但是作用的高峰出现在注射后6min。胆碱能受体拮抗剂阿托品可阻断ACh的作用。结论海马CA1区内的胆碱能神经元和毒蕈碱受体参与了伤害性信息的处理,并且起到了镇痛作用。吗啡成瘾可以降低CA1区痛反应神经元对伤害性刺激的敏感性。     

帕金森病大鼠苍白球神经元簇发放电及峰峰间期序列的研究

目的 观察帕金森病大鼠模型苍白球神经元的电活动.方法 30只大鼠注射6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)建立PD模型,并通过跑步机测试、注射阿朴吗啡诱发旋转和免疫组化检测黑质对模型进行评价;10只大鼠注射含0.2%抗坏血酸的人工脑脊液建立对照组.在立体定向仪引导下记录大鼠在PD病理及正常生理状态下GP神经元的自发放电活动.结果 模型组大鼠中有13只行为学及病理学检测结果符合PD模型标准.电生理记录显示对照组大鼠GP神经元放电频率为(6.04±2.12)Hz,模型组大鼠GP神经元放电频率为(21.10±3.21)Hz(P=0.001).模型组GP神经元簇发放电模式的比例术后4周为59%,术后8周为61%,而对照组GP神经元簇发放电模式的比例在术后4周和8周均为11%.模型组大鼠神经元放电的峰峰间期散点图在100ms以下有一分布密集条带.结论 PD模型大鼠GP神经元较生理状态下放电频率明显增加,簇状放电模式比例增大,ISI序列发生明显变化.     

Excitatory effects of dopamine on subthalamic nucleus neurons: in vitro study of rats pretreated with 6-hydroxydopamine and levodopa

Increased output from the subthalamic nucleus (STN) following chronic dopamine depletion has been linked to the rigidity and tremor seen in Parkinson's disease (PD). We used extracellular microelectrode recordings from rat brain slices to investigate effects of dopamine on STN neurons. In brain slices prepared from rats that received unilateral 6-hydroxydopamine (6-OHDA) treatment, the spontaneous firing rate of STN neurons was reduced by 63%, and the firing pattern was more irregular, compared to STN neurons from normal rats. However, treatment with levodopa (50 mg/kg, i.p., daily) for 4 weeks normalized the firing rate and pattern of STN neurons in the 6-OHDA-treated rats. Dopamine (3-300 microM), added to the superfusate, significantly increased the firing rates of STN neurons in a concentration-dependent fashion, and also produced a more regular firing pattern in 6-OHDA-lesioned tissue. This excitatory effect of dopamine was mimicked by a D2 receptor agonist (quinpirole), and was reduced by the D2 antagonists haloperidol, clozapine and sulpiride. Antagonists of the D1 receptor (SCH-23390) and ionotropic glutamatergic receptors (CNQX and AP5) could not block the effect of dopamine on firing rate. These results suggest that dopamine exerts a direct excitatory influence on STN neurons via the activation of D2-like receptors.     

Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity.

The influence of subthalamic nucleus (STN) afferents on dopaminergic (DA) neurons of the rat substantia nigra (SN) was investigated. Hemisections of the brain placed between the STN and the SN or located anterior to the STN caused an increase in the firing rate of DA cells without producing significant changes in their firing pattern. In contrast, electrolytic and ibotenic acid lesions of the STN resulted in 93% and 49% reductions, respectively, in the level of burst firing without affecting the firing rate of DA cells recorded in the lateral SN. Furthermore, procedures which interrupted the STN input to the SN produced rapid pacemaker-like firing in 18% of the lateral SN DA neurons recorded. Activation of the STN using single pulses of electrical stimulation caused: 1) a 20-50 msec inhibition of DA cell firing followed by an excitation, which in 35% of DA cells was accompanied by spikes occurring in a burst-like pattern, and 2) a short-latency inhibition lasting 5-25 msec in 75% of non-DA SN zona reticulata (ZR) neurons. On the other hand, stimulation of the STN for 1 minute at 20 Hz resulted in an initial decrease in DA cell burst firing followed by elevated firing rates and increased burst firing by 30-60 minutes after the stimulation. Pharmacological activation of the STN by infusion of bicuculline caused a rapid inhibition of DA cells followed by a two-fold increase in burst firing 6-14 minutes later, whereas SN ZR cells responded with an elevation in firing rate which dissipated in 6-14 minutes. Muscimol-induced STN inhibition produced complimentary biphasic changes in SN neuron firing: 1) an initial increase followed by a decrease in burst firing and firing rate of DA neurons and 2) a rapid inhibition followed by an excitation of ZR cells over a similar time course. Thus, the STN appears to exert a dual action on SN DA cells: 1) initial inhibition possibly mediated through STN excitation of the inhibitory SN ZR projections to DA cells, and 2) a facilitation of burst firing which may be a direct effect of excitatory STN afferents.     

Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat

The pallido-subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep-wake cycle, single-unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non-anaesthetized head-restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1-2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical 'direct/indirect' model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.     

Dopamine lesion-induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats

Dysfunctional activity in the subthalamic nucleus (STN) is thought to underlie movement deficits of patients with Parkinson's disease. Alterations in STN firing patterns are also evident in the anesthetized rat model of Parkinson's disease, where studies show that loss of striatal dopamine and concomitant changes in the indirect pathway are associated with bursty and oscillatory firing patterns in STN output. However, the extent to which alterations in cortical activity contribute to changes in STN activity is unclear. As pyramidal neurons in the cingulate cortex project directly to the STN, cingulate output was assessed after dopamine lesion by simultaneously recording single-unit and local field potential (LFP) activities in STN and anterior cingulate cortex in control, dopamine-lesioned and non-lesioned hemispheres of urethane-anesthetized rats. Correlated oscillations were observed in cross-correlograms of spike trains from STN and cingulate layer V neurons with broad waveforms indicative of pyramidal neurons. One-2 weeks after dopamine cell lesion, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of neurons and LFP power in the STN all increased significantly. In contrast, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of cingulate layer V putative pyramidal neurons and power in cingulate LFPs did not differ significantly between dopamine-lesioned, non-lesioned or control hemispheres, despite significant loss of dopamine in the lesioned cingulate cortex. Data show that alterations in STN activity in the dopamine-lesioned hemisphere are not associated with alterations in neuronal activity in layer V of the anterior cingulate cortex in anesthetized rats.     

Effects of 6-hydroxydopamine-induced severe or partial lesion of the nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in the rat

The origin of changes in the neuronal activity of the globus pallidus (GP) and the subthalamic nucleus (STN) in animal models of Parkinson's disease (PD) is still controversial. The aim of the study was to investigate the neuronal activity of STN and GP neurons under urethane anesthesia in an early and in an advanced stage PD rat model. 6-Hydroxydopamine (6-OHDA) injection into the striatum induced a partial lesion of dopamine cells in the substantia nigra pars compacta (SNc) and fibers in the striatum. The GP firing rate decreased significantly with no significant change of the pattern. 6-OHDA injection into the SNc induced a total or subtotal lesion without any change in the firing rate and patterns of GP neurons. Concerning the STN, after partial lesion, the firing rate remained unchanged but the firing pattern significantly changed towards a more irregular and bursty pattern. In rats with total or subtotal lesion of the SNc the firing rate increased significantly and the relative amount of tonic neurons significantly decreased. Our results demonstrate that neuronal reactivity in the basal ganglia network considerably differs in the early versus late stage model of PD. We showed that the pathological activity of STN neurons after severe lesion is not mediated by the GP. Moreover, the unchanged activity of GP neurons is likely to be a consequence of the STN hyperactivity. These data suggest that in the GP-STN-GP network, the excitatory influence of the STN-GP pathway overrides that of the GABAergic GP-STN pathway, questioning the classical model of basal ganglia organization.     

Time-course of changes in firing rates and firing patterns of subthalamic nucleus neuronal activity after 6-OHDA-induced dopamine depletion in rats

The subthalamic nucleus (STN) plays a key role in motor control. Disorganization of its neuronal activity is implicated in the manifestation of parkinsonian motor symptoms. The aim of the present work was to study the time-course of changes in the firing activity of STN neurons in a rat model of parkinsonism. Electrophysiological recordings were done in normal rats and four groups of rats at different time points after 6-hydroxydopamine (6-OHDA) microinjection into the pars compacta of substantia nigra (SNc). Results showed a significant decrease in firing rate during the first and second weeks post lesion (5.53+/-0.56 and 7.66+/-0.73 spikes/s, respectively) compared to normal rats (11.13+/-0.59 spikes/s). From the 3rd week after 6-OHDA injection the firing rates returned toward baseline, with an average of 9.71+/-0.51 spikes/s during the 3rd week and 11.13+/-0.71 spikes/s during the 4th week. With regard to firing pattern, the majority of STN cells (90%) discharged regularly or slightly irregularly in normal animals. Only 4% exhibited burst activity and 6% had mixed firing patterns. After SNc-lesion, the percentage of cells exhibiting burst and mixed patterns increased progressively from 35% during the first week to 56% at week 4 post-lesion. In sum, these experiments revealed that the firing rate of STN neurons was altered only transiently following nigral lesions, whereas a progressive and stable change in the firing pattern was observed up to 4 weeks post lesion, suggesting that the persistence of bursts firing more closely relates to the motor pathologies of this rat model of parkinsonism.     

Complex EPSCs evoked in substantia nigra reticulata neurons are disrupted by repetitive stimulation of the subthalamic nucleus

Although substantia nigra reticulata (SNR) neurons fire bursts of action potentials during normal movement, excessive burst firing correlates with symptoms of Parkinson's disease. A major excitatory output from the subthalamic nucleus (STN) to the SNR is thought to provide the synaptic impetus for burst firing in SNR neurons. Using patch pipettes to record from SNR neurons in rat brain slices, we found that a single electrical stimulus delivered to the STN evokes a burst of action potentials. Under voltage-clamp conditions, STN stimulation evokes a complex EPSC that is comprised of an initial monosynaptic EPSC followed by a series of late EPSCs superimposed on a long-lasting inward current. Using varied stimulation frequencies, we found that the initial EPSC was significantly reduced or abolished after 2 s of 50-100 Hz STN stimulation. However, only 4 s of 1 Hz stimulation was required to abolish the late component of the complex EPSC. We suggest that differential effects of repetitive STN stimulation on early and late components of complex EPSCs may help explain the frequency-dependent effects of deep brain stimulation of the STN that is used in the treatment of Parkinson's disease.     

Effects of various frequency electrical stimulation of the dorsal raphe nucleus on spontaneous firing activities in the rat subthalamic nucleus★

BACKGROUND： Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus （STN） neurons in the rat brain. OBJECTIVE： To validate the effect of electrical stimulation to the dorsal raphe nucleus （DRN） on the neuronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies. DESIGN, TIME AND SETTING： Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design. MATERIALS： Twenty-four healthy male Sprague-Dawley （SD） rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Company （USA）; a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS： Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinson＇s disease, rats in the model group were injected with 4μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group received deep brain stimulation in same brain region without modeling. Electrical stimulation （width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds） was delivered to the DRN. MAIN OUTCOME MEASURES： The firing rates of STN neurons were observed by extracellular recording using a biological signal acquisition system. RESULTS： DRN-high-frequency stimulation （DRN-HFS） induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from （7.14±0.75） and （7.94 ± 0.61） Hz to （11.17 ±1.49） and （12.11 ± 1.05） Hz, respectively （P 〈 0.01）. Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dep     

Glutamatergic-receptors blockade does not regularize the slow wave sleep bursty pattern of subthalamic neurons

The subthalamic nucleus (STN) has been implicated in movement disorders observed in Parkinson's disease because of its pathological mixed burst firing mode and hyperactivity. In physiological conditions, STN bursty pattern has been shown to be dependent on slow wave cortical activity. Indeed, cortical ablation abolished STN bursting activity in urethane-anaesthetized intact or dopamine depleted rats. Thus, glutamate afferents might be involved in STN bursting activity during slow wave sleep (SWS) when thalamic and cortical cells oscillate in a low-frequency range. The present work was aimed to test, on non-anaesthetized rats, if it was possible to regularize the SWS STN bursty pattern by microiontophoresis of kynurenate, a broad-spectrum glutamate ionotropic receptors antagonist. As glutamatergic effects might be masked by GABAergic inputs arriving tonically and during the entire sleep-wake cycle on STN neurons, kynurenate was also co-iontophoresed with bicuculline, a GABA(A) receptors antagonist. Kynurenate iontophoretic applications had a weak inhibitory effect on the discharge rate of STN neurons whatever the vigilance state, and did not regularize the SWS STN bursty pattern. But, the robust bursty bicuculline-induced pattern was impaired by kynurenate, which elicited the emergence of single spikes between remaining bursts. These data indicate that the bursty pattern exhibited by STN neurons specifically in SWS, does not seem to exclusively depend on glutamatergic inputs to STN cells. Furthermore, GABA(A) receptors may play a critical role in regulating the influence of excitatory inputs on STN cells.     

Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is a neurosurgical alternative to medical treatment in levodopa-responsive forms of Parkinson disease. The mechanism of action of STN stimulation remains controversial, although an inhibition of overactive STN neurons has been postulated. OBJECTIVE: To determine the effects of high-frequency STN stimulation on the neuronal activity of STN neurons in Parkinson disease patients. PATIENTS: Single-unit recordings of the neuronal activity of the STN were obtained before, during, and after the application of intra-STN electrical stimulation in 15 Parkinson disease patients. Changes in firing frequency and pattern were analyzed using various combinations of stimulus frequency (range, 14-140 Hz). RESULTS: Stimulation at a frequency greater than 40 Hz applied within the STN significantly decreased the firing frequency and increased the burst-like activity in the firing pattern of STN neurons. An aftereffect was observed in cells that had been totally inhibited during high-frequency stimulation. CONCLUSION: The beneficial effects of high-frequency stimulation result from a change in the firing pattern of cellular discharge and a blockade of the spontaneous overactivity of STN neurons.