丘脑底核电刺激对大鼠黑质网状部及苍白球细胞外神经递质的影响

目的 通过电刺激正常及癫痫大鼠丘脑底核(STN),研究黑质网状部(SNr)及苍白球(GP)细胞外液中谷氨酸(Glu)、γ-氨基丁酸(GABA)的变化,探讨电刺激治疗癫痫的机制.方法 正常大鼠和癫痫大鼠各加只,将刺激电极植入一侧STN,分别用130 Hz和260 Hz进行刺激,同时在同侧的SNr和GP收集细胞外液,用高压液相色谱法检测其Glu和GABA的含量.结果 癫痫大鼠SNr的GABA基础值明显高于正常大鼠.电刺激使两组SNr的GABA明显升高.130 Hz和260 Hz刺激明显增高两组GP和SNr的Glu含量,但130 Hz的更显著.结论 SNr细胞外GABA升高在STN电刺激治疗中起重要作用.电刺激增加了GP细胞的活动,STN电刺激治疗癫痫机制不能单纯解释为"功能的毁损".     

Neurochemical mechanisms induced by high frequency stimulation of the subthalamic nucleus: increase of extracellular striatal glutamate and GABA in normal and hemiparkinsonian rats

High frequency stimulation (HFS) (130 Hz) of the subthalamic nucleus (STN) provides beneficial effects in patients suffering from severe parkinsonism, but the mechanisms underlying these clinical results remain to be clarified. To date, very little is known concerning the effects of STN-HFS on neurochemical transmission in the different basal ganglia nuclei and in particular the striatum. This study examines the effects of STN-HFS in intact and hemiparkinsonian rats on extracellular striatal glutamate (Glu) and GABA levels by means of intracerebral microdialysis. Unilateral STN-HFS was found to induce a significant bilateral increase of striatal Glu and GABA both in intact and in dopamine-lesioned animals. In intact rats, these increases were reversed by local administration of the D1 antagonist SCH 23390, but were potentiated by the D2 antagonist sulpiride. Potentiation was also observed after local administration of both D1 and D2 antagonists whose amplitude was similar to that measured in hemiparkinsonian rats. These data furnish the first evidence that STN-HFS influences striatal amino-acid transmission and that this influence is modulated by dopamine. They provide evidence that the effects of STN-HFS are not only restricted to the direct STN targets, but also involve adaptive changes within other structures of the basal ganglia circuitry.     

Effect of electrical and chemical stimulation of the subthalamic nucleus on the release of striatal dopamine

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, but the mechanisms underlying these clinical results remain to be clarified. The HFS of STN is associated with the release of dopamine (DA) in the striatum. This study examines possible mechanisms by which HFS-STN release DA. The experiments were performed in rats anesthetized with urethane. The STN was stimulated by electrical HF and chemical microinjections of an antagonist and an agonist of GABA(A) receptors, the bicuculline, and the muscimol, respectively. The extracellular striatal DA-DOPAC (3-4-dihydroxyphenilacetic acid) content was collected by means of intracerebral microdialysis cannula and analyzed with HPLC with an electrochemical detector. The HFS of STN and microinjection of bicuculline intrasubthalamic produced a significant increase of extracellular striatal DA, whereas DOPAC levels were unchanged. The microinjection of muscimol depresses spontaneous release of DA, without changes in DOPAC. The kainic acid lesion of the globus pallidus (GP) and the substantia nigra pars reticulata (SNr), ipsilateral to dialyzed striatum, did not modify the release of DA-DOPAC. These data provide evidence that the STN has a tonic action on the substantia nigra pars compacta (SNc), and the release of striatal DA by HFS-STN may be due to activation of the STN acting directly on SNc neurons.     

Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.     

High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat

High frequency stimulation (HFS) of the subthalamic nucleus (STN) can partially alleviate motor symptoms in patients with Parkinson's disease (PD). However, the mechanism of action of HFS is incompletely understood. We investigated the effect of HFS (130 Hz) and low frequency stimulation (LFS, 20 Hz) of the STN on striatal dopaminergic transmission and metabolism using in vivo microdialysis in anaesthetized and freely moving rats. While LFS had no effect, HFS of the STN produced a delayed, stable and intensity-dependent increase of extracellular dopamine metabolites. Striatal extracellular levels of dopamine and 5-HIAA were not influenced by HFS or LFS in the present experimental paradigm. We conclude that HFS of the STN influences striatal dopaminergic metabolism in naive, nonlesioned rats.     

Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease

To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92-3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs.     

High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats

The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats.     

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...     

High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats,but less efficiency in a choice reaction time task

Chronic subthalamic nucleus high frequency stimulation (STN HFS) improves motor function in Parkinson's disease. However, its efficacy on cognitive function and the mechanisms involved are less known. The aim of this study was to assess the effects of STN HFS in hemiparkinsonian awake rats performing different specific motor tests and a cognitive operant task. Unilateral STN HFS applied in unilaterally DA-depleted rats decreased the apomorphine-induced circling behaviour and reduced catalepsy induced by the neuroleptic haloperidol. DA-depleted rats exhibited severe deficits in the operant task, among which the inability to perform the task was not alleviated by STN HFS. However, in a few animals showing less impairment, STN HFS significantly reduced the contralateral neglect induced by the lesion. These results are the first to demonstrate a beneficial effect of STN HFS applied in awake rats on basic motor functions. However, STN HFS appears to be less effective on impaired cognitive functions.     

电刺激丘脑底核对大鼠杏仁核电点燃的抑制作用

目的 在大鼠杏仁核电点燃癫痫模型中研究丘脑底核高频深部电刺激对点燃的抑制作用及其对Glu、GABA浓度的影响.方法 建立大鼠杏仁核电刺激点燃模型,观察丘脑底核高频深部电刺激对点燃发作的抑制作用,应用高效液相色谱（HPLC）测定大鼠脑组织中Glu、GABA的浓度.结果 对丘脑底核高频深部电刺激（130 Hz,0.2 ms,5 V）能够有效抑制大鼠杏仁核电点燃（P＜0.05）;并可以降低纹状体内Glu浓度,升高纹状体内GABA浓度（P＜0.05）.结论 丘脑底核高频深部脑电刺激能有效抑制大鼠杏仁核电点燃,其作用机制可能与改变Glu、GABA浓度平衡有关.     

A combined in vivo neurochemical and electrophysiological analysis of the effect of high-frequency stimulation of the subthalamic nucleus on 5-HT transmission

Movement disability in advanced Parkinson's disease (PD) can be treated by high frequency stimulation (HFS) of the subthalamic nucleus (STN) but some patients experience psychiatric side-effects including depression, which is strongly linked to decreases in 5-hydroxytryptamine (5-HT). The current study investigated the effect of bilateral STN HFS on extracellular 5-HT in brain regions of anesthetized and freely moving rats as measured with microdialysis. Parallel in vivo electrophysiological experiments allowed a correlation of changes in extracellular 5-HT with the firing of 5-HT neurons. Bilateral STN HFS decreased (by up to 25%) extracellular levels of 5-HT in both striatum and medial prefrontal cortex of anesthetized rats. STN HFS also decreased extracellular 5-HT in the medial prefrontal cortex of freely moving rats. This decrease in extracellular 5-HT persisted after turning off the stimulation, and was present in dopamine-denervated rats. As with changes in extracellular 5-HT, in anesthetized rats STN HFS evoked a decrease in the in vivo firing of midbrain raphe 5-HT neurons that also persisted after cessation of stimulation. These data provide neurochemical evidence for an inhibition of 5-HT neurotransmission by STN HFS, which may contribute to its psychiatric side effects and guide therapeutic options.     

The effects of electrode material, charge density and stimulation duration on the safety of high-frequency stimulation of the subthalamic nucleus in rats

High-frequency stimulation (HFS) of deep brain structures is a powerful therapeutic tool for the treatment of various movement disorders in patients. However, the pathophysiological mechanisms of this therapeutic approach on basal ganglia network function are still largely unknown. Hitherto, experimental studies have focused on short-term stimulation. Since patients receive HFS for many years, animal studies which reproduce the conditions of long-term stimulation will be necessary to accurately investigate the effects of HFS. However, stimulation parameters of acute HFS cannot be easily transferred to long-term conditions. Accordingly, for this purpose we studied the influence of different charge densities (0, 3, 6.5, 13 and 26 microC/cm2/phase) and duration (4 h or 3 days) of subthalamic nucleus (STN)-HFS using stainless-steel and platinum-iridium (Pt/Ir) electrodes on neuronal tissue damage in rats. Our data demonstrate the advantage of Pt/Ir over stainless-steel electrodes when used in short-term HFS (frequency 130 Hz, pulse width 60 micros) and indicate that HFS using Pt/Ir-electrodes pulsed with 3 microC/cm2/phase over 3 days did not produce any relevant tissue damage in the STN.     

Behavioral effects of high frequency electrical stimulation of the hippocampus on electrical kindling in rats

Experiments were designed to evaluate the effects of high frequency electrical stimulation (HFS) applied in ventral hippocampus during the hippocampal kindling process, as well as on the expression of fully kindled seizures and the refractoriness for subsequent convulsions during their postictal period. Male Wistar rats, stereotactically implanted in both ventral hippocampus, received daily bilateral HFS (pulses of 60 micros width at 130 Hz at subthreshold current intensity) during 1h immediately after each kindling stimulation (1s train of 60 Hz biphasic square waves, each 1 ms) during 40 days or until the kindled state was achieved. Rats were classified as follows: (a) Responder animals, who required low current intensity for HFS (208+/-38.2 microA), did not show progress of the kindling process and remained in stages II and III seizures. (b) Nonresponders rats, in which the current intensity for HFS was higher (434.5+/-51.7 microA), developed the kindling process as the kindling control group. When HFS was applied before the kindling stimulation in fully kindled rats, animals presented a reduced expression of the fully kindled seizures (nonresponders animals) and an enhanced refractoriness for subsequent seizures during the postictal period (kindling control and nonresponder animals). There was no correlation between the area where the HFS was applied and the effects induced. It was concluded that HFS at 130 Hz in ventral hippocampus is able to modify the epileptogenesis induced by the hippocampal kindling process and the refractoriness to subsequent seizures during the postictal period in rats.     

Controlling seizures is not controlling epilepsy: a parametric study of deep brain stimulation for epilepsy

Pharmacological inhibition and high-frequency stimulation (HFS) of the substantia nigra pars reticulata (SNr) suppress seizures in different animal models of epilepsy. The aim of the present study was to determine the optimal parameters of HFS to control spontaneous seizures in a genetic model of absence epilepsy in the rat. Single SNr stimulation that was bilateral, bipolar and monophasic at 60 Hz frequency and with 60-micros pulse width was optimal. However, when used for repeated stimulations, long-term suppression did not occur and even the number of seizures increased. A delay of at least 60 s between stimulations was necessary to be fully effective. Although single HFS of the SNr can be used to suppress ongoing seizures, repeated HFS is ineffective and could even aggravate seizures in our model. Thus investigations of accurate stimulation procedures are still needed.     

High frequency stimulation of the subthalamic nucleus increases c-fos immunoreactivity in the dorsal raphe nucleus and afferent brain regions

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson’s disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.     

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     

Future prospects of brain stimulation

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim has replaced thalamotomy as a treatment of tremor of various origins and was extended to two other targets (Subthalamic nucleus (STN) and the medial pallidus (GPi)), since 1993 based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then suppresses also levodopa induced dyskinesias. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. The effects remain stable over more than five years chronic HFS of STN, as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsies. It is therefore possible that DAS in STN as well as in other targets could become a potent therapeutic tool in the future for neurological disorders. The future of brain stimulation will depend on new technologies (new circuits, electrodes, web based programmers), waveforms (alternatives to square waves, random distribution), targets (hypothalamic nuclei, locus coeruleus) and indications (dystonia, epilepsy, eating disorders.     

Transsynaptic cell death of neurons following striatopallidal lesions does not occur in substantia nigra pars reticulata in developing rats

In adult rats, combined lesions of the striatum and globus pallidus (GP) cause transsynaptic cell death of neurons in the substantia nigra pars reticulata (SNr) which becomes apparent 1–2 weeks after the lesions. This delayed cell death of SNr neurons has been explained to be caused by over-excitation of SNr neurons which results from an imbalance between excitatory and inhibitory inputs due to two simultaneous events: acceleration of the excitatory input from the disinhibited subthalamic nucleus (STN) and deprivation of the inhibitory input from the striatum. To examine whether the transsynaptic neuronal death in SNr is caused by the same lesions in developing rats, we destroyed the striatum and GP in rats on postnatal days 10 (P10), P15, P20, P25, P30, P35 and P60 by injecting ibotenic acid. We found that cell death did not occur in SNr neurons in rats younger than P20 and that Fos expression induced in STN neurons after these striatopallidal lesions in P10 and P20 rats was lower than that in P30 or P60 rats. These findings suggest that excitation of STN neurons is not enough to cause cell death of SNr neurons in rats younger than P20. Immature functional connection between the cerebral cortex and STN in the early developing animals may contribute to the resistivity of SNr neurons to transsynaptic delayed cell death.     

High‐frequency stimulation of the subthalamic nucleus modulates neuronal activity in the lateral habenula nucleus

High‐frequency stimulation (HFS) of the subthalamic nucleus (STN) is often used to treat movement disability in advanced Parkinson's disease, but some patients experience debilitating psychiatric effects including depression. Interestingly, HFS of the STN modulates 5‐HT neurons in the dorsal raphe nucleus (DRN) which are linked to depression, but the neural substrate of this effect is unknown. Here, we tested the effect of STN stimulation on neuronal activity in the lateral habenula nucleus (LHb), an important source of input to DRN 5‐HT neurons and also a key controller of emotive behaviours. LHb neurons were monitored in anaesthetized rats using single‐unit extracellular recording, and localization within the LHb was confirmed by juxtacellular labelling. HFS of the STN (130 Hz) evoked rapid changes in the firing rate of the majority of LHb neurons tested (38 of 68). Some LHb neurons (19/68) were activated by HFS, while others (19/68), distinguished by a higher basal firing rate, were inhibited. LHb neurons that project to the DRN were identified using antidromic activation and collision testing (n = 17 neurons). Some of these neurons (5/17) were also excited by HFS of the STN, and others (7/17) were inhibited although this was only a statistical trend. In summary, HFS of the STN modulated the firing of LHb neurons, including those projecting to the DRN. The data identify that the STN impacts on the LHb‐DRN pathway. Moreover, this pathway may be part of the circuitry mediating the psychiatric effects of STN stimulation experienced by patients with Parkinson's disease.     

Frequency matters: beta‐band subthalamic nucleus deep‐brain stimulation induces Parkinsonian‐like blink abnormalities in normal rats

The synchronized beta‐band oscillations in the basal ganglia‐cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta‐band activity in PD motor symptoms by testing the effects of beta‐frequency subthalamic nucleus deep‐brain stimulation (STN DBS) on the blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6‐hydroxydopamine lesions and patients with PD. These deficits were not an artifact of STN DBS because, when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate that the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta‐band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz STN DBS exaggerated the blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency‐specific STN DBS can be used to create PD‐like or dystonic‐like symptoms in a normal rat.