The Anterior Globus Pallidus Externus of Basal Ganglia as Primarily a Limbic and Associative Territory

The mammalian brain is composed of diverse, specialized cell populations, few of which we fully understand. To more systematically ascertain and learn from cellular specializations in the brain, we used Drop-seq to perform single-cell RNA sequencing of 690,000 cells sampled from nine regions of the adult mouse brain: frontal and posterior cortex (156,000 and 99,000 cells, respectively), hippocampus (113,000), thalamus (89,000), cerebellum (26,000), and all of the basal ganglia – the striatum (77,000), globus pallidus externus/nucleus basalis (66,000), entopeduncular/subthalamic nuclei (19,000), and the substantia nigra/ventral tegmental area (44,000). We developed computational approaches to distinguish biological from technical signals in single-cell data, then identified 565 transcriptionally distinct groups of cells, which we annotate and present through interactive online software we developed for visualizing and re-analyzing these data (DropViz). Comparison of cell classes and types across regions revealed features of brain organization. These included a neuronal gene-expression module for synthesizing axonal and presynaptic components; widely shared patterns in the combinatorial co-deployment of voltage-gated ion channels by diverse neuronal populations; functional distinctions among cells of the brain vasculature; and specialization of glutamatergic neurons across cortical regions to a degree not observed in other neuronal or non-neuronal populations. We describe systematic neuronal classifications for two complex, understudied regions of the basal ganglia, the globus pallidus externus and substantia nigra reticulata. In the striatum, where neuron types have been intensely researched, our data reveal a previously undescribed population of striatal spiny projection neurons (SPNs) comprising 4% of SPNs. The adult mouse brain cell atlas can serve as a reference for analyses of development, disease, and evolution.

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Indirect pathway of caudate tail for choosing good objects in periphery

10.1101/547232 ◽

2019 ◽

Author(s):

Hidetoshi Amita ◽

Okihide Hikosaka

Keyword(s):

Basal Ganglia ◽

Globus Pallidus ◽

Real Life ◽

Inhibitory Response ◽

Choice Task ◽

Local Injection ◽

Indirect Pathway ◽

Rejection Mechanism ◽

Goal Directed Behavior ◽

Globus Pallidus Externus

AbstractChoosing good objects is essential for real life, which is controlled mainly by the basal ganglia. For that, a subject need to not only find good objects, but ‘reject’ bad objects. To reveal this ‘rejection’ mechanism, we created a sequential saccade choice task for monkeys and studied the indirect pathway of caudate tail mediated by cvGPe (caudal-ventral globus pallidus externus). The inhibitory responses of cvGPe neurons to bad objects were smaller when the monkey made saccades to them by mistake. Moreover, experimental reduction of the inhibitory response by local injection of bicuculline (GABAA antagonist) disabled the monkey to reject bad objects. In conclusion, rejecting bad objects is crucial for goal-directed behavior, which is controlled by the indirect pathway in the basal ganglia.

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Astrocytic Regulation of Basal Ganglia Dopamine/D2-Dependent Behaviors

10.1101/2021.05.11.443394 ◽

2021 ◽

Author(s):

Rosa Mastrogiacomo ◽

Gabriella Trigilio ◽

Daniel Dautan ◽

Celine Devroye ◽

Valentina Ferretti ◽

...

Keyword(s):

Basal Ganglia ◽

Globus Pallidus ◽

Sensorimotor Gating ◽

D2 Receptors ◽

Dopamine D2 Receptors ◽

Dopamine D2 ◽

Dopaminergic Tone ◽

Globus Pallidus Externus

Astrocytic involvement in dopamine dynamics related to motivational and sensorimotor gating abilities is unknown. We found that dysbindin-1 (Dys1) hypofunction increases the activity of as-trocytes, which express only the isoform Dys1A that is reduced in the caudate of patients with schizophrenia. Astrocytic Dys1A disruption resulted in avolition and sensorimotor gating deficits, increased astrocytic dopamine D2 receptors and decreased dopaminergic tone within basal gan-glia. Notably, astrocytic Dys1A hypofunction disrupted dopamine dynamics linked to reward ex-pectancy and interconnected with astrocytes Ca2+ responses mainly in the globus pallidus externus (GPe). Finally, we proved these phenotypes were mediated by D2 receptors in astrocytes as their selective deletion in astrocytes either in GPe or SNc/VTA enhanced motivation and sensorimotor gating abilities as well as dopaminergic release in the GPe. Therefore, astrocytes control motivational and sensorimotor gating processes through Dys1A/D2-dependent mechanisms within the basal ganglia.

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Morphological Abnormalities in the Basal Ganglia of Dystonia Patients

Stereotactic and Functional Neurosurgery ◽

10.1159/000512599 ◽

2021 ◽

pp. 1-12

Author(s):

Xi Bai ◽

Peter Vajkoczy ◽

Katharina Faust

Keyword(s):

Basal Ganglia ◽

Globus Pallidus ◽

Trajectory Planning ◽

Matched Control ◽

Young Patients ◽

Control Population ◽

Pathogenic Role ◽

Target Region ◽

Morphological Abnormalities ◽

Primary Dystonia

Objective: The pathophysiology of dystonia is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperinstensive signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare. Methods: Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients. Results: There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients <25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group. Conclusions: BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear.

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Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog

Development ◽

10.1242/dev.125.24.5079 ◽

1998 ◽

Vol 125 (24) ◽

pp. 5079-5089 ◽

Cited By ~ 15

Author(s):

J.D. Kohtz ◽

D.P. Baker ◽

G. Corte ◽

G. Fishell

Keyword(s):

Basal Ganglia ◽

Globus Pallidus ◽

Sonic Hedgehog ◽

Adult Brain ◽

Ganglionic Eminence ◽

Lateral Ganglionic Eminence ◽

Expression Characteristic ◽

Sonic Hedgehog Gene ◽

Embryonic Structure ◽

Sequential Induction

The cortex and basal ganglia are the major structures of the adult brain derived from the embryonic telencephalon. Two morphologically distinct regions of the basal ganglia are evident within the mature ventral telencephalon, the globus pallidus medially, and the striatum, which is positioned between the globus pallidus and the cortex. Deletion of the Sonic Hedgehog gene in mice indicates that this secreted signaling molecule is vital for the generation of both these ventral telencephalic regions. Previous experiments showed that Sonic Hedgehog induces differentiation of ventral neurons characteristic of the medial ganglionic eminence, the embryonic structure which gives rise to the globus pallidus. In this paper, we show that later in development, Sonic Hedgehog induces ventral neurons with patterns of gene expression characteristic of the lateral ganglionic eminence. This is the embryonic structure from which the striatum is derived. These results suggest that temporally regulated changes in Sonic Hedgehog responsiveness are integral in the sequential induction of basal telencephalic structures.

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Two Pathways Between the Cortex and the Basal Ganglia Output Nuclei and the Globus Pallidus

Advances in Behavioral Biology - The Basal Ganglia V ◽

10.1007/978-1-4899-0194-1_9 ◽

1996 ◽

pp. 77-94 ◽

Cited By ~ 6

Author(s):

Hitoshi Kita

Keyword(s):

Basal Ganglia ◽

Globus Pallidus

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Disrupted basal ganglia—thalamocortical loops in focal to bilateral tonic-clonic seizures

10.1101/618215 ◽

2019 ◽

Author(s):

Xiaosong He ◽

Ganne Chaitanya ◽

Burcu Asma ◽

Lorenzo Caciagli ◽

Danielle S. Bassett ◽

...

Keyword(s):

Basal Ganglia ◽

Temporal Lobe Epilepsy ◽

Globus Pallidus ◽

Temporal Lobe ◽

Functional Organization ◽

Globus Pallidus Internus ◽

Effective Control ◽

Thalamocortical Connections ◽

Clonic Seizures ◽

Current History

AbstractFocal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

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Effects of Dopamine Depletion on Network Entropy in the External Globus Pallidus

Journal of Neurophysiology ◽

10.1152/jn.00344.2009 ◽

2009 ◽

Vol 102 (2) ◽

pp. 1092-1102 ◽

Cited By ~ 36

Author(s):

Ana V. Cruz ◽

Nicolas Mallet ◽

Peter J. Magill ◽

Peter Brown ◽

Bruno B. Averbeck

Keyword(s):

Basal Ganglia ◽

Globus Pallidus ◽

Dopamine Depletion ◽

Information Coding ◽

Logistic Regression Models ◽

Firing Rates ◽

Before And After ◽

Network Entropy ◽

Coding Capacity

Dopamine depletion in cortical-basal ganglia circuits in Parkinson's disease (PD) grossly disturbs movement and cognition. Classic models relate Parkinsonian dysfunction to changes in firing rates of basal ganglia neurons. However, disturbances in other dynamics of neural activity are also common. Taking both inappropriate firing rates and other dynamics into account and determining how changes in the properties of these neural circuits that occur during PD impact on information coding are thus imperative. Here, we examined in vivo network dynamics in the external globus pallidus (GPe) of rats before and after chronic dopamine depletion. Dopamine depletion led to decreases in the firing rates of GPe neurons and increases in synchronized network oscillations in the β frequency (13–30 Hz) band. Using logistic regression models, we determined the combined and separate impacts of these factors on network entropy, a measure of the upper bound of information coding capacity. Importantly, changes in these features in dopamine-depleted rats led to a significant decrease in GPe network entropy. Changes in firing rates had the largest impact on entropy, with changes in synchrony also decreasing entropy at the network level. Changes in autocorrelations tended to offset these effects because autocorrelations decreased entropy more in the control animals. Thus it is possible that reduced information coding capacity within basal ganglia networks may contribute to the behavioral deficits accompanying PD.

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Subthalamo-Pallidal Circuit

Handbook of Brain Microcircuits ◽

10.1093/med/9780190636111.003.0013 ◽

2017 ◽

pp. 143-150

Author(s):

Charles J. Wilson

Keyword(s):

Basal Ganglia ◽

Substantia Nigra ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Substantia Nigra Pars Reticulata ◽

Modern Methods

The subthalamo-pallidal system constitutes the second layer of circuitry in the basal ganglia, downstream of the striatum. It consists of four nuclei. Two of them, the external segment of the globus pallidus (GPe) and subthalamic nucleus (STN), make their connections primarily within the basal ganglia. The others, the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr), are the output nuclei of the basal ganglia. Collectively, their axons distribute collaterals to all the targets of the basal ganglia. Rare interneurons have been reported in each of them from studies of Golgi-stained preparations, but they have not so far been confirmed using more modern methods. The circuit as described here is based primarily on studies of the axonal arborizations of neurons stained individually by intracellular or juxtacellular labeling.

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