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.

Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method

2014 ◽  
Vol 112 (1) ◽  
pp. 120-146 ◽  
Author(s):  
Kenji Morita
Keyword(s):  
D2 Receptor ◽  
Computational Method ◽  
Cortical Activation ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Short Term ◽  
Apparent Contradiction ◽  
Striatal Projection Neurons ◽  
Cortical Inputs ◽  
Stimulation Of

The corticostriatal system is considered to be crucially involved in learning and action selection. Anatomical studies have shown that two types of corticostriatal neurons, intratelencephalic (IT) and pyramidal tract (PT) cells, preferentially project to dopamine D1 or D2 receptor-expressing striatal projection neurons, respectively. In contrast, an optogenetic study has shown that stimulation of IT axons evokes comparable responses in D1 and D2 cells and that stimulation of PT axons evokes larger responses in D1 cells. Since the optogenetic study applied brief stimulation only, however, the overall impacts of repetitive inputs remain unclear. Moreover, the apparent contradiction between the anatomical and optogenetic results remains to be resolved. I addressed these issues by using a computational approach. Specifically, I constructed a model of striatal response to cortical inputs, with parameters regarding short-term synaptic plasticity and anatomical connection strength for each connection type. Under the constraint of the optogenetic results, I then explored the parameters that best explain the previously reported paired-pulse ratio of response in D1 and D2 cells to cortical and intrastriatal stimulations, which presumably recruit different compositions of IT and PT fibers. The results indicate that 1) IT→D1 and PT→D2 connections are anatomically stronger than IT→D2 and PT→D1 connections, respectively, consistent with the previous findings, and that 2) IT→D1 and PT→D2 synapses entail short-term facilitation, whereas IT→D2 and PT→D1 synapses would basically show depression, and thereby 3) repetitive IT or PT inputs have larger overall impacts on D1 or D2 cells, respectively, supporting a recently proposed hypothesis on the roles of corticostriatal circuits in reinforcement learning.

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 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 Dopamine regulates distinctively the activity patterns of striatal output neurons in advanced parkinsonian primates

2015 ◽  
Vol 113 (5) ◽  
pp. 1533-1544 ◽  
Author(s):  
Arun Singh ◽  
Li Liang ◽  
Yoshiki Kaneoke ◽  
Xuebing Cao ◽  
Stella M. Papa
Keyword(s):  
Basal Ganglia ◽  
Firing Pattern ◽  
Activity Patterns ◽  
Receptor Activation ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Response Compatible ◽  
Motor Abnormalities ◽  
The Impact

Nigrostriatal dopamine denervation plays a major role in basal ganglia circuitry disarray and motor abnormalities of Parkinson's disease (PD). Studies in rodent and primate models have revealed that striatal projection neurons, namely, medium spiny neurons (MSNs), increase the firing frequency. However, their activity pattern changes and the effects of dopaminergic stimulation in such conditions are unknown. Using single-cell recordings in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates with advanced parkinsonism, we studied MSN activity patterns in the transition to different motor states following levodopa administration. In the “off” state (baseline parkinsonian disability), a burst-firing pattern accompanied by prolonged silences (pauses) was found in 34% of MSNs, and 80% of these exhibited a levodopa response compatible with dopamine D1 receptor activation (direct pathway MSNs). This pattern was highly responsive to levodopa given that bursting/pausing almost disappeared in the “on” state (reversal of parkinsonism after levodopa injection), although this led to higher firing rates. Nonbursty MSNs fired irregularly with marked pausing that increased in the on state in the MSN subset with a levodopa response compatible with dopamine D2 receptor activation (indirect pathway MSNs), although the pause increase was not sustained in some units during the appearance of dyskinesias. Data indicate that the MSN firing pattern in the advanced parkinsonian monkey is altered by bursting and pausing changes and that dopamine differentially and inefficiently regulates these behaviorally correlated patterns in MSN subpopulations. These findings may contribute to understand the impact of striatal dysfunction in the basal ganglia network and its role in motor symptoms of PD.

scholarly journals Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures

Brain ◽  
2021 ◽  
Author(s):  
Anastasia Brodovskaya ◽  
Shinnosuke Shiono ◽  
Jaideep Kapur
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
Frontal Lobe ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
D2 Receptor ◽  
Field Potential ◽  
Anticonvulsant Effect ◽  
Neuronal Activation ◽  
Indirect Pathway

Abstract There are no detailed descriptions of neuronal circuit active during frontal lobe motor seizures. Using activity reporter mice, local field potential recordings, tissue clearing, viral tracing, and super-resolution microscopy, we found neuronal activation after focal motor to bilateral tonic-clonic seizures in the striatum, globus pallidus externus, subthalamic nucleus, substantia nigra pars reticulata and neurons of the indirect pathway. Seizures preferentially activated dopamine D2 receptor-expressing neurons over D1 in the striatum, which have different projections. Furthermore, the D2 receptor agonist infused into the striatum exerted an anticonvulsant effect. Seizures activate structures via short and long latency loops, and anatomical connections of the seizure focus determine the seizure circuit. These studies, for the first time, show activation of neurons in the striatum, globus pallidus, subthalamic nucleus, and substantia nigra during frontal lobe motor seizures on the cellular level, revealing a complex neuronal activation circuit subject to modulation by the basal ganglia.

scholarly journals Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys

2012 ◽  
Vol 107 (5) ◽  
pp. 1500-1512 ◽  
Author(s):  
Arash Hadipour-Niktarash ◽  
Karen S. Rommelfanger ◽  
Gunasingh J. Masilamoni ◽  
Yoland Smith ◽  
Thomas Wichmann
Keyword(s):  
Basal Ganglia ◽  
Significant Proportion ◽  
D2 Receptor ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Electron Microscopic ◽  
Mediated Effects ◽  
Unmyelinated Axons ◽  
Electrophysiological Recordings

According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the “indirect” pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions.

Modern prevention and active longevity programs on the basis of disruptive domestic technologies: positive experience and prospects for application

2020 ◽  
pp. 66-73
Author(s):  
A. Simonova ◽  
S. Chudakov ◽  
R. Gorenkov ◽  
V. Egorov ◽  
A. Gostry ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Early Detection ◽  
Laboratory Diagnostics ◽  
Positive Experience ◽  
Practical Application ◽  
Wide Range ◽  
Integrated Program ◽  
Long Term Experience ◽  
Early Detection And Prevention

The article summarizes the long-term experience of practical application of domestic breakthrough technologies of preventive personalized medicine for laboratory diagnostics of a wide range of socially significant non-infectious diseases. Conceptual approaches to the formation of an integrated program for early detection and prevention of civilization diseases based on these technologies are given. A vision of the prospects for the development of this area in domestic and foreign medicine has been formed.

To the 70th anniversary of World Meteorological Organization. Scientific and technical cooperation of Hydrometeorological Center of the USSR/Russia in the Programs of World Meteorological Organization

2020 ◽  
pp. 117-138
Author(s):  
S.V. Borshch ◽  
◽  
R.M. Vil’fand ◽  
D.B. Kiktev ◽  
V.M. Khan ◽  
...  
Keyword(s):  
Environmental Monitoring ◽  
High Efficiency ◽  
World Meteorological Organization ◽  
70Th Anniversary ◽  
Technical Level ◽  
Technical Cooperation ◽  
Wide Range

The paper presents the summary and results of long-term and multi-faceted experience of international scientific and technical cooperation of Hydrometeorological Center of Russia in the field of hydrometeorology and environmental monitoring within the framework of WMO programs, which indicates its high efficiency in performing a wide range of works at a high scientific and technical level. Keywords: World Meteorological Organization, major WMO programs, representatives of Hydrometeorological Center of Russia in WMO

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