scholarly journals Physiology of Basal Ganglia Disorders: An Overview

1993 ◽  
Vol 20 (3) ◽  
pp. 177-183 ◽  
Author(s):  
Mark Hallett
Keyword(s):  
Basal Ganglia ◽  
Movement Disorders ◽  
Voluntary Movement ◽  
Good Theory ◽  
Indirect Pathway ◽  
Anatomy And Physiology ◽  
Direct Pathway ◽  
Motor Synergies ◽  
Recent Advances ◽  
Basal Ganglia Disorders

ABSTRACT:The pathophysiology of the movement disorders arising from basal ganglia disorders has been uncertain, in part because of a lack of a good theory of how the basal ganglia contribute to normal voluntary movement. An hypothesis for basal ganglia function is proposed here based on recent advances in anatomy and physiology. Briefly, the model proposes that the purpose of the basal ganglia circuits is to select and inhibit specific motor synergies to carry out a desired action. The direct pathway is to select and the indirect pathway is to inhibit these synergies. The clinical and physiological features of Parkinson's disease, L-DOPA dyskinesias, Huntington's disease, dystonia and tic are reviewed. An explanation of these features is put forward based upon the model.

#3101 Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntingtons disease: first evidence from human in vivo neuroimaging

2021 ◽  
Vol 92 (8) ◽  
pp. A6.1-A6
Author(s):  
Akshay Nair ◽  
Adeel Razi ◽  
Sarah Gregory ◽  
Robb Rutledge ◽  
Geraint Rees ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Bayesian Model ◽  
Empirical Bayes ◽  
Model Comparison ◽  
De Novo ◽  
Effective Connectivity ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Bayesian Model Comparison

BackgroundThe gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and inhibit movement respectively. In Huntingtons disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition that gives rise to the characteristic motor features of the condition. But early HD is also specifically associated with apathy, a failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively.MethodsUsing a novel technique for estimating dynamic effective connectivity of the basal ganglia, we tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD (n = 94). We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We used an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison.ResultsWith this fully Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway and by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component of our model.ConclusionsThe empirical evidence we provide here is the first in vivo demonstration that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

scholarly journals Key Modulatory Role of Presynaptic Adenosine A2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway

2009 ◽  
Vol 9 ◽  
pp. 1321-1344 ◽  
Author(s):  
César Quiroz ◽  
Rafael Luján ◽  
Motokazu Uchigashima ◽  
Ana Patrícia Simoes ◽  
Talia N. Lerner ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neuropsychiatric Disorders ◽  
Receptor Function ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Selective Modulation ◽  
Efferent Pathways

Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1and D2receptors, respectively. Adenosine A2Areceptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2Areceptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2Areceptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2Areceptors could provide a new target for the treatment of neuropsychiatric disorders.

scholarly journals Parallel Movement-suppressing Striatal Output Pathways

2020 ◽  
Author(s):  
Qiaoling Cui ◽  
Xixun Du ◽  
Isaac Y. M. Chang ◽  
Arin Pamukcu ◽  
Varoth Lilascharoen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Body Movement ◽  
Disease Model ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Striatal Projection Neurons ◽  
6 Hydroxydopamine

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

scholarly journals Multiple neuronal circuits for variable object–action choices based on short- and long-term memories

2019 ◽  
Vol 116 (52) ◽  
pp. 26313-26320 ◽  
Author(s):  
Okihide Hikosaka ◽  
Masaharu Yasuda ◽  
Kae Nakamura ◽  
Masaki Isoda ◽  
Hyoung F. Kim ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Basic Mechanism ◽  
Indirect Pathway ◽  
Value Judgment ◽  
Direct Pathway ◽  
Caudate Head ◽  
Parallel Circuits ◽  
Parallel Circuit ◽  
Short And Long Term

At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.

scholarly journals Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Konstantin I Bakhurin ◽  
Xiaoran Li ◽  
Alexander D Friedman ◽  
Nicholas A Lusk ◽  
Glenn DR Watson ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Reinforcement Schedule ◽  
Action Selection ◽  
Fixed Time ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Direct Pathway ◽  
Stimulation Of

The basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimulation of D1+ (direct) and A2A+ (indirect) neurons in the ventrolateral striatum in head-fixed mice on a fixed time reinforcement schedule. Direct pathway stimulation initiates licking, whereas indirect pathway stimulation suppresses licking and results in rebound licking after stimulation. Moreover, direct and indirect pathways also play distinct roles in timing. Direct pathway stimulation produced a resetting of the internal timing process, whereas indirect pathway stimulation transiently paused timing, and proportionally delayed the next bout of licking. Our results provide evidence for the continuous and opposing contributions of the direct and indirect pathways in the production and timing of reward-guided behavior.

scholarly journals Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways

2019 ◽  
Author(s):  
Konstantin I. Bakhurin ◽  
Xiaoran Li ◽  
Alexander D. Friedman ◽  
Nicholas A. Lusk ◽  
Glenn D.R. Watson ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Reinforcement Schedule ◽  
Action Selection ◽  
Fixed Time ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Direct Pathway ◽  
Stimulation Of

AbstractThe basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimulation of D1+ (direct) and A2A+ (indirect) neurons in the ventrolateral striatum in head-fixed mice on a fixed time reinforcement schedule. Direct pathway stimulation initiates licking, whereas indirect pathway stimulation suppresses licking and results in rebound licking after stimulation. Moreover, direct and indirect pathways also play distinct roles in timing. Direct pathway stimulation produced a resetting of the internal timing process, whereas indirect pathway stimulation transiently paused timing, and proportionally delayed the next bout of licking. Our results provide evidence for the continuous and opposing contributions of the direct and indirect pathways in the production and timing of reward-guided behavior.

scholarly journals Direct pathway neurons in mouse dorsolateral striatum in vivo receive stronger synaptic input than indirect pathway neurons

2019 ◽  
Vol 122 (6) ◽  
pp. 2294-2303 ◽  
Author(s):  
Marko Filipović ◽  
Maya Ketzef ◽  
Ramon Reig ◽  
Ad Aertsen ◽  
Gilad Silberberg ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Basal Ganglia ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Potential Fluctuations ◽  
Direct Pathway ◽  
Spiny Neurons ◽  
Total Input ◽  
Membrane Potential Fluctuations

Striatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1- or D2-type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modeling of the striatal network has predicted that under healthy conditions dMSNs should receive more total input than iMSNs. To test this prediction, we analyzed in vivo whole cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (6OHDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials, we found that dMSNs depolarized toward the spike threshold significantly faster than iMSNs did. Together, these findings (in particular the STA analysis) corroborate the theoretical prediction that direct-pathway MSNs receive stronger total input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question of how the lack of dopamine may lead to behavioral deficits associated with Parkinson’s disease. NEW & NOTEWORTHY The direct and indirect pathways of the basal ganglia originate from the D1- and D2-type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs). Theoretical results have predicted that dMSNs should receive stronger synaptic input than iMSNs. Using in vivo intracellular membrane potential data, we provide evidence that dMSNs indeed receive stronger input than iMSNs, as has been predicted by the computational model.

Pathophysiology of Basal Ganglia Disorders

CNS Spectrums ◽  
1998 ◽  
Vol 3 (2) ◽  
pp. 36-40 ◽  
Author(s):  
Jau-Shin Lou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Surgical Treatment ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Movement Disorders ◽  
Normal State ◽  
Dopaminergic Neurons ◽  
Basal Ganglia Disorders

AbstractParkinson's disease is the most common basal ganglia disorder that is caused by the degeneration of dopaminergic neurons in the substantia nigra. This article reviews the normal physiology of the basal ganglia in the normal state, as well as the pathophysiology of Parkinson's disease (PD) and other movement disorders associated with the basal ganglia. Also discussed is the pathophysiological basis for the surgical treatment of PD.

scholarly journals Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntington's disease

2021 ◽  
Author(s):  
Akshay Nair ◽  
Adeel Razi ◽  
Sarah Gregory ◽  
Robb R Rutledge ◽  
Geraint Rees ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Bayesian Model ◽  
Empirical Bayes ◽  
Model Comparison ◽  
De Novo ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Bayesian Model Comparison

The gating of movement depends on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways - the direct and indirect basal ganglia pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is thought to encourage and inhibit movement respectively. In Huntington's disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition giving rise to the characteristic motor features of the condition. But early HD is also associated with apathy, a loss of motivation and failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively. We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD. Using an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison. With this automated Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway components of our model and, by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component. The empirical evidence we provide here is demonstrates that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

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