A computational model of Parkinsonian handwriting that highlights the role of the indirect pathway in the basal ganglia

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.

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Modeling Basal Ganglia for Understanding Parkinsonian Reaching Movements

Neural Computation ◽

10.1162/neco_a_00073 ◽

2011 ◽

Vol 23 (2) ◽

pp. 477-516 ◽

Cited By ~ 30

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.

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ACE (Actor-Critic-Explorer) Paradigm for Reinforcement Learning in Basal Ganglia: Highlighting the Role of the Indirect Pathway

Advances in Cognitive Science ◽

10.4135/9788132107910.n6 ◽

2014 ◽

pp. 71-90

Author(s):

Denny Joseph ◽

Garipelli Gangadhar ◽

V. Srinivasa Chakravarthy

Keyword(s):

Reinforcement Learning ◽

Basal Ganglia ◽

Indirect Pathway

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Understanding Parkinsonian Handwriting Through a Computational Model of Basal Ganglia

Neural Computation ◽

10.1162/neco.2008.03-07-498 ◽

2008 ◽

Vol 20 (10) ◽

pp. 2491-2525 ◽

Cited By ~ 19

Author(s):

Garipelli Gangadhar ◽

Denny Joseph ◽

V. Srinivasa Chakravarthy

Keyword(s):

Basal Ganglia ◽

Computational Model ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Line Contour ◽

Velocity Fluctuations ◽

Signaling Model ◽

Tip Velocity ◽

Handwriting Generation

Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease.

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Indirect pathway from caudate tail mediates rejection of bad objects in periphery

Science Advances ◽

10.1126/sciadv.aaw9297 ◽

2019 ◽

Vol 5 (8) ◽

pp. eaaw9297 ◽

Cited By ~ 5

Author(s):

Hidetoshi Amita ◽

Okihide Hikosaka

Keyword(s):

Basal Ganglia ◽

Choice Task ◽

Inhibitory Influence ◽

Indirect Pathway ◽

Crucial Component ◽

Rejection Mechanism ◽

Everyday Task ◽

Goal Directed Behavior ◽

Globus Pallidus Externus

The essential everyday task of making appropriate choices is a process controlled mainly by the basal ganglia. To this end, subjects need not only to find “good” objects in their environment but also to reject “bad” objects. To reveal this rejection mechanism, we created a sequential saccade choice task for monkeys and studied the role of the indirect pathway from the CDt (tail of the caudate nucleus) mediated by cvGPe (caudal-ventral globus pallidus externus). Neurons in cvGPe were typically inhibited by the appearance of bad objects; however, this inhibition was reduced on trials when the monkeys made undesired saccades to the bad objects. Moreover, disrupting the inhibitory influence of CDt on cvGPe by local injection of bicuculline (GABAA receptor antagonist) impaired the monkeys’ ability to suppress saccades to bad objects. Thus, the indirect pathway mediates the rejection of bad choices, a crucial component of goal-directed behavior.

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