High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions

Shi, L.H.; Woodward, Donald J.; Luo, Fei; Anstrom, Kristin K.; Schallert, Timothy; Chang, Jing Yu

doi:10.1016/j.brainres.2004.03.053

Cited by 62 publications

(39 citation statements)

References 36 publications

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“…This is the first description, to our knowledge, of a behavioral role for a subpopulation of neurons within the STN. Our results are comparable to those obtained by traditional methods of lesioning this nucleus, in which animals display a consistent improvement in locomotion (35), and also clearly observed in experiments with high-frequency stimulation of the STN (36,37). Although we cannot determine whether disabling Vglut2-expressing neurons is necessary for this behavioral effect, we now have evidence that it is a sufficient condition.…”

Section: Discussionsupporting

confidence: 72%

Limiting glutamate transmission in a Vglut2 -expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

Schweizer

Pupe

Arvidsson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knockout mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.Parkinson disease | deep brain stimulation | vesicular transporter | optogenetics | striatum T he subthalamic nucleus (STN) has long been a structure of interest for researchers and clinicians alike. There is ample evidence that high-frequency stimulation of the STN improves symptoms such as tremor, rigidity, and slowness of movement, so called bradykinesia, in patients with Parkinson disease (see ref. 1 for review), but the mechanism through which this is achieved is still unknown. Some studies suggest that electrical stimulation causes a hyperexcitation of this structure (2), whereas others find evidence that the opposite is true (3-5). Other possible interpretations include the activation of the zona incerta, a neighboring white-matter structure (6) or of fibers coming from the motor cortex (7). Bilateral lesions of the STN improve locomotion (8), a result that is consistent with the inactivation hypothesis. However, previous studies have also found cognitive side effects when using high-frequency stimulation of the STN (9), findings supported by lesion studies in experimental animals, which led to abnormalities in operant tasks involving attention and impulsivity (10, 11). The projections of the STN to other regions help explain the multiple roles of this structure: It sends projections to other targets in the basal ganglia, such as the internal segment of the globus pallidus [also termed the entopeduncular nucleus (EP) in rodents] and the substantia nigra pars reticulata (SNr) (12, 13). The STN is also part of a circuit that includes the prefrontal cortex and the nucleus accumbens (14). It is currently unknown, however, whether these different roles reflect a heterogeneous population of cells, characterized by distinct gene expression. If that is the case, it would allow direct control over each cell population, facilitating the investigation of their respective roles. In rodents, the S...

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Section: Discussionsupporting

confidence: 72%

Limiting glutamate transmission in a Vglut2 -expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

Schweizer

Pupe

Arvidsson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The consequences of STN-DBS in 6-OHDA hemiparkinsonian rats have been previously studied by several authors [58][59][60][61][62][63]. As in the case of the PPTg-DBS, the results were not unequivocal on the various parameters investigated.…”

Section: Comparison With Stn-dbsmentioning

confidence: 83%

“…Moreover, in sham-operated animals, STN-DBS per se significantly reduced correct responses and also induced perseverative behaviours [59]. In contrast to these negative outcomes, STN-DBS improved treadmill locomotion in unilaterally 6-OHDA-lesioned rats [60], shortened RT in a simple task in rats whose dorsolateral part of the striatum received bilateral 6-OHDA lesions [61] and improved the use of the contralateral forelimb in the cylinder wall touching test in rats bearing a unilateral nigrostriatal DA lesion [62].…”

Section: Comparison With Stn-dbsmentioning

confidence: 90%

Continuous stimulation of the pedunculopontine tegmental nucleus at 40Hz affects preparative and executive control in a delayed sensorimotor task and reduces rotational movements induced by apomorphine in the 6-OHDA parkinsonian rat

Capozzo¹,

Vitale²,

Mattei³

et al. 2014

Behavioural Brain Research

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“…The A/G148 polymorphism has been associated with variations in total and LDL-C levels, FPG levels, and birth weight (Hegele et al, 1997(Hegele et al, , 1998. The polymorphism at position 311 has been associated with coronary artery disease, ischemic stroke in patients with type 2 diabetes mellitus, late-onset Alzheimer's disease, and reduced bone mass in postmenopausal women (Kao et al, 2002;Chen et al, 2003;Yamada et al, 2003;Martinelli et al, 2004;Shi et al, 2004). Our study showed that the PON2 C allele is a significant risk factor for CAAD in the Xinjiang Han and Uighur people with hypertension.…”

Section: Discussionmentioning

confidence: 99%

Association of paraoxonase polymorphisms with carotid artery atherosclerosis in essential hypertension patients

Han¹,

Xu²,

Xue³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. We investigated the relationships between paraoxonase genetic polymorphisms and essential hypertension in carotid artery atherosclerotic patients. The study included 353 Han participants and 240 Uighur participants from Xinjiang; they were further divided into two groups: essential hypertension with carotid artery atherosclerosis (CAAD group) and essential hypertension without carotid artery atherosclerosis (control group). Genotypes were detected by PCR, followed by restriction analyses with specific endonucleases. In Han people, the M allele frequency was significantly higher in the CAAD group than in the control group. The CC/CS genotype and C allele frequencies were significantly higher in the CAAD group than in the control group. Logistic regression analysis demonstrated that PON1 55M allele [odds ratio (OR) = 1.889] and PON2 311C allele (OR = 1.692) are independent risk factors for CAAD. Combined genotype analysis showed that PON1 55M and PON2 311C alleles are independent risk 5175 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (4): 5174-5185 (2013) Atherosclerosis in essential hypertension patients factors for CAAD (OR = 1.428). In the Uighur population, the CC/ CS genotype and C allele frequencies were significantly higher in the CAAD group than in the control group. Logistic regression analysis demonstrated that the PON2 311C allele is an independent risk factor for CAAD. We conclude that the PON1 55M and PON2 311C alleles are independent risk factors for CAAD in essential hypertension patients from the Xinjiang Han population. We also conclude that the PON2 311C allele is a risk factor for CAAD in essential hypertension patients from the Xinjiang Uighur population.

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High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions

Cited by 62 publications

References 36 publications

Limiting glutamate transmission in a Vglut2 -expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

Limiting glutamate transmission in a Vglut2 -expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

Continuous stimulation of the pedunculopontine tegmental nucleus at 40Hz affects preparative and executive control in a delayed sensorimotor task and reduces rotational movements induced by apomorphine in the 6-OHDA parkinsonian rat

Association of paraoxonase polymorphisms with carotid artery atherosclerosis in essential hypertension patients

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