scholarly journals Connectivity and Functionality of the Globus Pallidus Externa Under Normal Conditions and Parkinson's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Jie Dong ◽  
Sarah Hawes ◽  
Junbing Wu ◽  
Weidong Le ◽  
Huaibin Cai

The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex connections with the other basal ganglia nuclei and brain regions. Recently, with the adoption of sophisticated genetic tools, substantial advances have been made in understanding the distinct molecular, anatomical, electrophysiological, and functional properties of GPe neurons and non-neuronal cells. Impairments in dopamine transmission in the basal ganglia contribute to Parkinson's disease (PD), the most common movement disorder that severely affects the patients' life quality. Altered GPe neuron activity and synaptic connections have also been found in both PD patients and pre-clinical models. In this review, we will summarize the main findings on the composition, connectivity and functionality of different GPe cell populations and the potential GPe-related mechanisms of PD symptoms to better understand the cell type and circuit-specific roles of GPe in both normal and PD conditions.

2019 ◽  
Vol 11 (2) ◽  
pp. 30-36
Author(s):  
A. G. Trufanov ◽  
A. A. Yurin ◽  
A. B. Buriak ◽  
S. A. Sandalov ◽  
M. M. Odinak ◽  
...  

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and the first one among the nosological entities of parkinsonism. Susceptibility-weighted imaging (SWI), magnetic resonance imaging (MRI) pulse sequence, which allows the in vivo estimation of the values of iron deposition in different areas of the brain, is a potential technique for the early diagnosis of PD and for the study of the pathogenesis of its complications.Objective: to compare the values of iron deposition in the basal ganglia in Stages II and III PD and to determine the relationship of clinical findings to the level of iron deposition according to the SWI findings.Patients and methods. Twenty-four patients with Hoehn and Yahr Stages II (n=24) and III (n=12) PD were examined. All the patients underwent brain MRI on a Siemens TrioTim (3T) MRI scanner by using pulse sequences T1, T2, SWI and subsequently quantifying the iron deposition (SPIN software). The accumulation of iron is visualized as an area of reduced signal intensity on SWI, and its estimation in accordance with the SPIN program has accordingly a smaller value. The regions of interest on both sides were the dentate nucleus, substantia nigra, red nucleus, putamen, globus pallidus, and head of the caudate nucleus. The examination protocol also included tests using the following scales: the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Examination (MMSE), Frontal Assessment Batter (FAB), Freezing of Gait (FOG), Gait and Balance Scale (GABS), the Epworth Daytime Sleepiness Scale, the Parkinson's Disease Quality of Life Questionnaire (PDQ), the Beck Depression Inventory, and the Clock-Drawing Test.Results and discussion. The investigators found significant (p<0.05) correlations between the clinical picture and the level of iron deposition in the regions of interest in patients with Stage II PD: FOG – left caudate nucleus (r=-0.94); GABS – left caudate nucleus (r=-0.94); and in patients with stage III of the disease: UPDRS (full) – left red nucleus (r=-0.82), right globus pallidus (r=-0,80), left putamen (r=-0,96); UPDRS (Section 2) – left red nucleus (r=-0.77), left globus pallidus (r=-0.84); UPDRS (Section 3) – right putamen (r=-0,85), right globus pallidus (r=-0.78), left globus pallidus (r=-0,92); FOG – left globus pallidus (r=-0.81); GABS – left red nucleus (r=-0.96), left putamen (r=0.82), right putamen (r=-0.89), left globus pallidus (r=-0.82), right globus pallidus (r=-0.85), left caudate nucleus (r=-0.82), right caudate nucleus (r=-0.89); Beck Depression Inventory – right substantia nigra (r=-0.82).Conclusion. SWI measurement of the values of iron deposition in the structures of the extrapyramidal system in PD provides an additional insight into the pathological processes occurring in them.


Author(s):  
Mark Guttman

ABSTRACT:The study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.


2013 ◽  
Vol 25 (12) ◽  
pp. 1953-1961 ◽  
Author(s):  
Marcos Hortes N. Chagas ◽  
Ila M.P. Linares ◽  
Giovana Jorge Garcia ◽  
Jaime E.C. Hallak ◽  
Vitor Tumas ◽  
...  

ABSTRACTBackground:Depression is the most common psychiatric manifestation in patients with Parkinson's disease (PD). In addition, depressive symptoms may be considered to be a prodromal manifestation of PD. In recent years, the association between PD and depression has been the focus of neuroimaging studies using functional and structural techniques.Methods:The aim of this study was to review the main neuroimaging studies assessing the comorbidity between depression and PD. Literature searches were conducted to find the major neuroimaging studies that consider primarily the comorbidity between depression and PD using the indices Web of Science and Lilacs.Results:In total, 296 papers were identified, and 18 of these studies were selected for the current review. The principal neuroimaging technique used was SPECT. The structural neuroimaging studies that have evaluated the impact of current or previous bouts of depression on the neurodegenerative process of PD are scarce and inclusive. The instruments that were used to evaluate depression differed among the studies. Several brain regions appear to be involved in depression, particularly the limbic system and the basal ganglia. In addition, the serotonergic, dopaminergic, and noradrenergic systems also appear to be associated with depressive symptoms in PD.Conclusion:Several brain regions and neurotransmitter systems are involved in depression in PD; however, the variety of criteria used to evaluate depressive symptoms precludes more specific conclusions.


2021 ◽  
Author(s):  
Kingshuk Chakravarty ◽  
Sangheeta Roy ◽  
Aniruddha Sinha ◽  
Atsushi Nambu ◽  
Satomi Chiken ◽  
...  

AbstractThe basal ganglia (BG) are crucial for a variety of motor and cognitive functions. Changes induced by persistent low-dopamine (e.g. in Parkinson’s disease), result in aberrant changes in steady-state population activity (β-band oscillations) and transient response of the BG. Typically, brief cortical stimulation results in a triphasic response in the substantia nigra pars reticulata (SNr, output of the BG). The properties of the triphasic responses are shaped by dopamine levels. While it is relatively well understood how changes in BG result in aberrant steady state activity, it is not clear which BG interactions are crucial for the aberrant transient responses in the BG. Moreover, it is also not clear whether the same or different mechanisms underlie the aberrant changes in steady-state activity and aberrant transient response. Here we used numerical simulations of a network model of BG to identify the key factors that determine the shape of the transient responses. We show that an aberrant transient response of the SNr in low-dopamine state, involves changes in both, the direct pathway and the recurrent interactions within the globus pallidus externa (GPe) and between GPe and sub-thalamic nucleus. We found that the connections from D2-type spiny projection neurons to GPe are most crucial in shaping the transient response and by restoring them to their healthy level, we could restore the shape of transient response even in low-dopamine state. Finally, we show that the changes in BG that result in aberrant transient response are also sufficient to generate pathological oscillatory activity.Significance statementTo understand how changes induced by low-dopamine (e.g. in Parkinson’s disease, PD) affect basal ganglia (BG) function, we need to identify the factors that determine the shape of BG responses to brief cortical stimuli. We show that transient response of the BG is also affected by recurrent interactions within the subnuclei of the BG, and not just feedforward pathways. We found that input and local connectivity within the globus pallidus externa are crucial for shaping the transient response. We also show that the same network changes may underlie both, pathological β-band oscillations and aberrant transient responses. Our results highlight the importance of the recurrent connectivity within the BG and provide a coherent view of emergence of pathological activity in PD.


Complexity ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuanhong Bi ◽  
Quansheng Liu ◽  
Jingyi Zhao ◽  
Wuritu Yang

Exploring the behaviors of beta oscillations in the basal ganglia is helpful to understand the mechanism of Parkinson’s disease. Studies have shown that the external and internal segments (GPe, GPi) of the globus pallidus receive different intensities of signals from the striatum in Parkinson’s disease and play different roles in the production of beta oscillations, but the relevant mechanism still remains unclear. Based on a model of the subthalamic nucleus (STN) and globus pallidus (GP), we propose an extended STN-GPe-GPi model and analyze the dynamical behaviors of beta oscillations in this model. The stability condition is obtained through theoretical analyses, and the generation of beta oscillations by the inputs from the cortex and striatum is further considered. The influence of some parameters related to GPi on its firing rate oscillations is discussed. The results obtained in this paper are expected to play a guiding role in the medical treatment of Parkinson’s disease.


2017 ◽  
Author(s):  
Amin Mirzaei ◽  
Arvind Kumar ◽  
Daniel Leventhal ◽  
Nicolas Mallet ◽  
Ad Aertsen ◽  
...  

AbstractBrief epochs of beta oscillations have been implicated in sensorimotor control in the basal ganglia of task-performing healthy animals. However, which neural processes underlie their generation and how they are affected by sensorimotor processing remains unclear. To determine the mechanisms underlying transient beta oscillations in the local field potential (LFP), we combined computational modeling of the subthalamo-pallidal network for the generation of beta oscillations with realistic stimulation patterns derived from single unit data. The single unit data were recorded from different basal ganglia subregions in rats performing a cued choice task. In the recordings we found distinct firing patterns in the striatum, globus pallidus and subthalamic nucleus related to sensory and motor events during the behavioral task. Using these firing patterns to generate realistic inputs to our network model lead to transient beta oscillations with the same time course as the rat LFP data. In addition, our model can account for further non-intuitive aspects of beta modulation, including beta phase resets following sensory cues and correlations with reaction time. Overall, our model can explain how the combination of temporally regulated sensory responses of the subthalamic nucleus, ramping activity of the subthalamic nucleus, and movement-related activity of the globus pallidus, leads to transient beta oscillations during behavior.Significance StatementTransient beta oscillations emerge in the normal functioning cortico-basal ganglia loop during behavior. In this work we employ a unique approach connecting a computational model closely with experimental data. In this way we achieve a simulation environment for our model that mimics natural input patterns in awake behaving animals. Using this approach we demonstrate that a computational model for beta oscillations in Parkinson’s disease can also account for complex patterns of transient beta oscillations in healthy animals. Therefore, we propose that transient beta oscillations in healthy animals share the same mechanism with pathological beta oscillations in Parkinson’s disease. This important result connects functional and pathological roles of beta oscillations in the basal ganglia.


2020 ◽  
Author(s):  
Luke A Johnson ◽  
Joshua E Aman ◽  
Ying Yu ◽  
David Escobar Sanabria ◽  
Jing Wang ◽  
...  

AbstractAbnormal oscillatory neural activity in the basal ganglia is thought to play a pathophysiological role in Parkinson’s disease. Many patient studies have focused on beta frequency band (13-35 Hz) local field potential activity in the subthalamic nucleus, however increasing evidence points to alterations in neural oscillations in high frequency ranges (>100 Hz) having pathophysiological relevance. Prior studies have found that power in subthalamic high frequency oscillations (HFOs) is positively correlated with dopamine tone and increased during voluntary movements, implicating these brain rhythms in normal basal ganglia function. Contrary to this idea, in the current study we present a combination of clinical and preclinical data that support the hypothesis that HFOs in the internal globus pallidus (GPi) are a pathophysiological feature of Parkinson’s disease. Spontaneous and movement-related pallidal field potentials were recorded from deep brain stimulation (DBS) leads targeting the GPi in five externalized Parkinson’s disease patients, on and off dopaminergic medication. We identified a prominent oscillatory peak centered at 200-300 Hz in the off-medication rest recordings in all patients. High frequency power increased during movement, and the magnitude of modulation was negatively correlated with bradykinesia. Moreover, high frequency oscillations were significantly attenuated in the on-medication condition, suggesting they are a feature of the parkinsonian condition. To further confirm that GPi high frequency oscillations are characteristic of dopamine depletion, we also collected field potentials from DBS leads chronically implanted in three rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). High frequency oscillations and their modulation during movement were not prominent in the normal condition but emerged in the parkinsonian condition in the monkey model. These data provide the first evidence demonstrating that exaggerated, movement-modulated high frequency oscillations in the internal globus pallidus are a pathophysiological feature of Parkinson’s disease, and motivate additional investigations into the functional roles of high frequency neural oscillations across the basal ganglia-thalamocortical motor circuit and their relationship to motor control in normal and diseased states. These findings also provide rationale for further exploration of these signals for electrophysiological biomarker-based device programming and stimulation strategies in patients receiving deep brain stimulation therapy.


2020 ◽  
Author(s):  
Seyed-Mojtaba Alavi ◽  
Amin Mirzaei ◽  
Alireza Valizadeh ◽  
Reza Ebrahimpour

Abstract Parkinson’s disease (PD) is associated with abnormal b band oscillations (13-30 Hz) in the cortico-basal ganglia circuits.Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN)and globus pallidus externa (GPe), due to the loss of dopamine, are accounted as the potential sources of b oscillations in thebasal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological boscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understoodand, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computationalnetwork model of basal ganglia which consists STN, GPe, globus pallidus interna (GPi), and thalamus neuronal population.This model can capture healthy and pathological b oscillations as what has been observed in experimental studies. Using thismodel, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that theexcitatory DBS (EDBS) is able to quench the pathological synchrony and b oscillations, while, applying inhibitory DBS (IDBS)failed to quench the PD signs. In addition, the EDBS ameliorated the thalamic activity related to tremor in the model, while,the IDBS outperformed. However, with the help of the model results, we conclude that the effect of the DBS on its target isexcitatory


1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.


Sign in / Sign up

Export Citation Format

Share Document