A direct projection from the subthalamic nucleus to the ventral thalamus in monkeys

Rico, Alberto J.; Barroso‐Chinea, Pedro; Conte-Perales, Lorena; Roda, Elvira; Gómez-Bautista, Virginia; Gendive, Miriam; Obeso, José A.; Lanciego, José L.

doi:10.1016/j.nbd.2010.05.004

Cited by 39 publications

(35 citation statements)

References 37 publications

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“…Another limitation is the fact that we also targeted some neurons in other parts of the brain, in particular the PH and the MN, even though neither area showed significantly reduced Vglut2 expression levels as detected by quantitative in situ hybridization. These structures are not traditionally associated with locomotion, and lesion studies also do not support a contributing role as to the phenotype of our cKO mice (39,40), but every manipulation can have unforeseeable consequences, and we cannot rule out that they are also involved in some of the results we reported. It is conceivable that our results could translate to other animals, and to humans as well.…”

Section: Discussionmentioning

confidence: 74%

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: Discussionmentioning

confidence: 74%

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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“…This study implies the STN to also receive inputs from the ventral visual stream, associated with the evaluation of stimuli used for action selection. Anatomically, the STN has been reported to intervene with the pallidum (Carpenter, Carleton, Keller, & Conte, 1981), thalamus (Rico et al, 2010), and cerebral cortex (Degos, Deniau, Le Cam, Mailly, & Maurice, 2008). At the same time, the STN is known to receive inputs (among others) from both pFC and BG nodes (Nambu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Visual Information Shapes the Dynamics of Corticobasal Ganglia Pathways during Response Selection and Inhibition

Jahfari¹,

Waldorp

Ridderinkhof

et al. 2015

Journal of Cognitive Neuroscience

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Action selection often requires the transformation of visual information into motor plans. Preventing premature responses may entail the suppression of visual input and/or of prepared muscle activity. This study examined how the quality of visual information affects frontobasal ganglia (BG) routes associated with response selection and inhibition. Human fMRI data were collected from a stop task with visually degraded or intact face stimuli. During go trials, degraded spatial frequency information reduced the speed of information accumulation and response cautiousness. Effective connectivity analysis of the fMRI data showed action selection to emerge through the classic direct and indirect BG pathways, with inputs deriving form both prefrontal and visual regions. When stimuli were degraded, visual and prefrontal regions processing the stimulus information increased connectivity strengths toward BG, whereas regions evaluating visual scene content or response strategies reduced connectivity toward BG. Response inhibition during stop trials recruited the indirect and hyperdirect BG pathways, with input from visual and prefrontal regions. Importantly, when stimuli were nondegraded and processed fast, the optimal stop model contained additional connections from prefrontal to visual cortex. Individual differences analysis revealed that stronger prefrontal-to-visual connectivity covaried with faster inhibition times. Therefore, prefrontal-to-visual cortex connections appear to suppress the fast flow of visual input for the go task, such that the inhibition process can finish before the selection process. These results indicate response selection and inhibition within the BG to emerge through the interplay of top-down adjustments from prefrontal and bottom-up input from sensory cortex.

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“…The pattern of axonal collateralization has served to identify up to five distinct types of STN efferent neurons Sato et al 2000). In addition to STN projections to the GPi, GPe, and SNr, efferent STN neurons also innervate thalamic targets: those projecting ipsilaterally to ventral thalamic motor nuclei (Nauta and Cole 1978;Rico et al 2010) and a smaller contralateral projection linking the STN with the parafascicular nucleus (Gerfen et al 1982;Castle et al 2005). Furthermore, dual retrograde tract-tracing studies have shown that subthalamic projections reaching the GPi and ventral thalamic nuclei largely arise from different subpopulations of STN neurons (Rico et al 2010).…”

Section: Subthalamic Nucleusmentioning

confidence: 99%

Functional Neuroanatomy of the Basal Ganglia

Lanciego

Luquin

Obeso

2012

Cold Spring Harbor Perspectives in Medicine

644

474

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The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.T he basal ganglia and related nuclei consist of a variety of subcortical cell groups engaged primarily in motor control, together with a wider variety of roles such as motor learning, executive functions and behavior, and emotions. The term basal ganglia in the strictest sense refers to nuclei embedded deep in the brain hemispheres (striatum or caudate-putamen and globus pallidus), whereas related nuclei consist of structures located in the diencephalon (subthalamic nucleus), mesencephalon (substantia nigra), and pons ( pedunculopontine nucleus). Ideas and concepts regarding the functions of the basal ganglia were strongly influenced by clinical observations during the 20th century, which showed that lesions of the lenticular nucleus ( putamen and globus pallidus) and the subthalamic nucleus (STN) were associated with parkinsonian signs, dystonia, and hemiballismus (Wilson 1925;Purdon-Martin 1927). Thus, the terms extra-pyramidal system and extra-pyramidal syndrome were frequently used in the past to refer to the pathological basis of movement disorders in an attempt to make a clear distinction from the pyramidal system (corticofugal neurons that give rise to corticospinal projections). At present, these terms and distinctions are considered obsolete and misleading and, therefore, will not be used in

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A direct projection from the subthalamic nucleus to the ventral thalamus in monkeys

Cited by 39 publications

References 37 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

Visual Information Shapes the Dynamics of Corticobasal Ganglia Pathways during Response Selection and Inhibition

Functional Neuroanatomy of the Basal Ganglia

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