scholarly journals The Enigmatic “Indirect Pathway” of the Basal Ganglia: A New Role

Neuron ◽  
2018 ◽  
Vol 99 (6) ◽  
pp. 1105-1107 ◽  
Author(s):  
Sten Grillner
Keyword(s):  
Basal Ganglia ◽  
Indirect Pathway

scholarly journals 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki ◽  
Miyuki Miyamoto ◽  
Yuka Ebihara ◽  
Kazutaka Shiomi ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Positron Emission Tomography ◽  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Emission Tomography ◽  
Fluorodeoxyglucose Positron Emission Tomography ◽  
Resonance Imaging ◽  
Indirect Pathway ◽  
Positron Emission ◽  
Fluorodeoxyglucose Positron Emission

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit.

Dynamic Changes in the Cortex-Basal Ganglia Network After Dopamine Depletion in the Rat

2008 ◽  
Vol 100 (1) ◽  
pp. 385-396 ◽  
Author(s):  
Cyril Dejean ◽  
Christian E. Gross ◽  
Bernard Bioulac ◽  
Thomas Boraud
Keyword(s):  
Basal Ganglia ◽  
Local Field ◽  
Signal Transmission ◽  
Local Field Potentials ◽  
Cellular Level ◽  
Cortical Activation ◽  
Field Potentials ◽  
Dopamine Depletion ◽  
Indirect Pathway ◽  
Before And After

It is well established that parkinsonian syndrome is associated with alterations in the temporal pattern of neuronal activity and local field potentials in the basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in parkinsonian patients and animal models of this disease. However, the mechanisms underlying this phenomenon remain unclear. This study investigates the functional connectivity in the cortex-BG network of a rodent model of Parkinson's disease. Single neurons and local field potentials were simultaneously recorded in the motor cortex, the striatum, and the substantia nigra pars reticulata (SNr) of freely moving rats, and high-voltage spindles (HVSs) were used to compare signal transmission before and after dopaminergic depletion. It is shown that dopaminergic lesion results in a significant enhancement of oscillatory synchronization in the BG: the coherence between pairs of structures increased significantly and the percentage of oscillatory auto- and cross-correlograms. HVS episodes were also more numerous and longer. These changes were associated with a shortening of the latency of SNr response to cortical activation, from 40.5 ± 4.8 to 10.2 ± 1.07 ms. This result suggests that, in normal conditions, SNr neurons are likely to be driven by late inputs from the indirect pathway; however, after the lesion, their shorter latency also indicates an overactivation of the hyperdirect pathway. This study confirms that neuronal signal transmission is altered in the BG after dopamine depletion but also provides qualitative evidence for these changes at the cellular level.

#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 Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons

2013 ◽  
Vol 33 (47) ◽  
pp. 18531-18539 ◽  
Author(s):  
B. S. Freeze ◽  
A. V. Kravitz ◽  
N. Hammack ◽  
J. D. Berke ◽  
A. C. Kreitzer
Keyword(s):  
Basal Ganglia ◽  
Projection Neurons ◽  
Indirect Pathway

scholarly journals Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Vincenzo G. Fiore ◽  
Francesco Rigoli ◽  
Max-Philipp Stenner ◽  
Tino Zaehle ◽  
Frank Hirth ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Standard Model ◽  
Sensory Input ◽  
Effective Connectivity ◽  
Individual Variability ◽  
Indirect Pathway ◽  
The Standard Model ◽  
Insight Into ◽  
New Framework ◽  
Deep Brain

Abstract Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.

Modeling the role of basal ganglia in saccade generation: Is the indirect pathway the explorer?

2011 ◽  
Vol 24 (8) ◽  
pp. 801-813 ◽  
Author(s):  
R. Krishnan ◽  
S. Ratnadurai ◽  
D. Subramanian ◽  
V.S. Chakravarthy ◽  
M. Rengaswamy
Keyword(s):  
Basal Ganglia ◽  
Indirect Pathway ◽  
Saccade Generation

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 Modeling Basal Ganglia for Understanding Parkinsonian Reaching Movements

2011 ◽  
Vol 23 (2) ◽  
pp. 477-516 ◽  
Author(s):  
K. N. Magdoom ◽  
D. Subramanian ◽  
V. S. Chakravarthy ◽  
B. Ravindran ◽  
Shun-ichi Amari ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Reaching Movements ◽  
Substantia Nigra Pars Compacta ◽  
Temporal Difference ◽  
Indirect Pathway ◽  
Dynamical Disease ◽  
Exploratory Movements ◽  
Dopamine Signal

We present a computational model that highlights the role of basal ganglia (BG) in generating simple reaching movements. The model is cast within the reinforcement learning (RL) framework with correspondence between RL components and neuroanatomy as follows: dopamine signal of substantia nigra pars compacta as the temporal difference error, striatum as the substrate for the critic, and the motor cortex as the actor. A key feature of this neurobiological interpretation is our hypothesis that the indirect pathway is the explorer. Chaotic activity, originating from the indirect pathway part of the model, drives the wandering, exploratory movements of the arm. Thus, the direct pathway subserves exploitation, while the indirect pathway subserves exploration. The motor cortex becomes more and more independent of the corrective influence of BG as training progresses. Reaching trajectories show diminishing variability with training. Reaching movements associated with Parkinson's disease (PD) are simulated by reducing dopamine and degrading the complexity of indirect pathway dynamics by switching it from chaotic to periodic behavior. Under the simulated PD conditions, the arm exhibits PD motor symptoms like tremor, bradykinesia and undershooting. The model echoes the notion that PD is a dynamical disease.

scholarly journals Endocannabinoids and Dopamine Balance Basal Ganglia Output

2021 ◽  
Vol 15 ◽  
Author(s):  
Lilach Gorodetski ◽  
Yocheved Loewenstern ◽  
Anna Faynveitz ◽  
Izhar Bar-Gad ◽  
Kim T. Blackwell ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Control Unit ◽  
Vital Role ◽  
Primary Afferents ◽  
Entopeduncular Nucleus ◽  
Indirect Pathway ◽  
Relay Nucleus ◽  
Prevailing View

The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.

scholarly journals A Dual Role Hypothesis of the Cortico-Basal-Ganglia Pathways: Opponency and Temporal Difference through Dopamine and Adenosine

2018 ◽  
Author(s):  
Kenji Morita ◽  
Yasuo Kawaguchi
Keyword(s):  
Basal Ganglia ◽  
Activity Patterns ◽  
D2 Receptor ◽  
Medium Spiny Neuron ◽  
Temporal Difference ◽  
Receptor Signaling ◽  
Indirect Pathway ◽  
Wide Range ◽  
Cortical Inputs

The hypothesis that the basal-ganglia direct and indirect pathways represent goodness (or benefit) and badness (or cost) of options, respectively, explains a wide range of phenomena. However, this hypothesis, named the Opponent Actor Learning (OpAL), still has limitations. Structurally, the OpAL model does not incorporate differentiation of the two types of cortical inputs to the basal-ganglia pathways received from intratelencephalic (IT) and pyramidal-tract (PT) neurons. Functionally, the OpAL model does not describe the temporal-difference (TD)-type reward-prediction-error (RPE), nor explains how RPE is calculated in the circuitry connecting to the DA neurons. In fact, there is a different hypothesis on the basal-ganglia pathways and DA, named the Cortico-Striatal-Temporal-Difference (CS-TD) model. The CS-TD model differentiates the IT and PT inputs, describes the TD-type RPE, and explains how TD-RPE is calculated. However, a critical difficulty in this model lies in its assumption that DA induces the same direction of plasticity in both direct and indirect pathways, which apparently contradicts the experimentally observed opposite effects of DA on these pathways. Here, we propose a new hypothesis that integrates the OpAL and CS-TD models. Specifically, we propose that the IT-basal-ganglia pathways represent goodness/badness of current options while the PT-indirect pathway represents the overall value of the previously chosen option, and both of these have influence on the DA neurons, through the basal-ganglia output, so that a variant of TD-RPE is calculated. A key assumption is that opposite directions of plasticity are induced upon phasic activation of DA neurons in the IT-indirect pathway and PT-indirect pathway because of different profiles of IT and PT inputs. Specifically, at PT→indirect-pathway-medium-spiny-neuron (iMSN) synapses, sustained glutamatergic inputs generate rich adenosine, which allosterically prevents DA-D2 receptor signaling and instead favors adenosine-A2A receptor signaling. Then, phasic DA-induced phasic adenosine, which reflects TD-RPE, causes long-term synaptic potentiation. In contrast, at IT→iMSN synapses where adenosine is scarce, phasic DA causes long-term synaptic depression via D2 receptor signaling. This new Opponency & Temporal-Difference (OTD) model provides unique predictions, part of which is potentially in line with recently reported activity patterns of neurons in the globus pallidus externus on the indirect pathway.

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