Role of striatal ΔFosB in l-Dopa–induced dyskinesias of parkinsonian nonhuman primates

Long-term dopamine (DA) replacement therapy in Parkinson’s disease (PD) leads to the development of abnormal involuntary movements known asl-Dopa–induced dyskinesia (LID). The transcription factor ΔFosB that is highly up-regulated in the striatum following chronicl-Dopa exposure may participate in the mechanisms of altered neuronal responses to DA generating LID. To identify intrinsic effects of elevated ΔFosB onl-Dopa responses, we induced transgenic ΔFosB overexpression in the striatum of parkinsonian nonhuman primates kept naïve ofl-Dopa treatment. Elevated ΔFosB levels led to consistent appearance of LID since the initial acutel-Dopa tests. In line with this motor response, striatal projection neurons (SPNs) responded to DA with changes in firing frequency that reversed at the peak of the motor response, and these unstable SPN activity changes in response to DA are typically associated with the emergence of LID. Transgenic ΔFosB overexpression also induced up-regulation of other molecular markers of LID. These results support an autonomous role of striatal ΔFosB in the adaptive mechanisms altering motor responses to chronic DA replacement in PD.

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Differences in synaptic integration between direct and indirect striatal projection neurons: Role of CaV 3 channels

Synapse ◽

10.1002/syn.22079 ◽

2018 ◽

Vol 73 (4) ◽

pp. e22079 ◽

Cited By ~ 2

Author(s):

Brisa García-Vilchis ◽

Paola Suárez ◽

Miguel Serrano-Reyes ◽

Mario Arias-García ◽

Dagoberto Tapia ◽

...

Keyword(s):

Synaptic Integration ◽

Projection Neurons ◽

Striatal Projection Neurons

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Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat

Journal of Neurophysiology ◽

10.1152/jn.00385.2014 ◽

2015 ◽

Vol 113 (3) ◽

pp. 796-807 ◽

Cited By ~ 7

Author(s):

Ricardo Hernández-Martínez ◽

José J. Aceves ◽

Pavel E. Rueda-Orozco ◽

Teresa Hernández-Flores ◽

Omar Hernández-González ◽

...

Keyword(s):

Receptor Agonist ◽

Projection Neurons ◽

Quantal Content ◽

Short Term ◽

Paired Pulse ◽

Short Term Plasticity ◽

Striatal Projection Neurons ◽

Muscarinic Cholinergic ◽

Muscarinic Modulation

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently.

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Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates

Cell Reports ◽

10.1016/j.celrep.2017.12.095 ◽

2018 ◽

Vol 22 (4) ◽

pp. 941-952 ◽

Cited By ~ 7

Author(s):

Arun Singh ◽

Meagan A. Jenkins ◽

Kenneth J. Burke ◽

Goichi Beck ◽

Andrew Jenkins ◽

...

Keyword(s):

Motor Response ◽

Projection Neurons ◽

Striatal Projection Neurons

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Dopamine D2 receptor-expressing striatal projection neurons display long term potentiation after high frequency stimulation of cortical afferents

Neuroscience Research ◽

10.1016/j.neures.2010.07.1508 ◽

2010 ◽

Vol 68 ◽

pp. e341

Author(s):

Cathy Ann Vickers ◽

Gordon Arbuthnott ◽

Jeff Wickens

Keyword(s):

Dopamine D2 Receptor ◽

D2 Receptor ◽

Long Term Potentiation ◽

High Frequency Stimulation ◽

Projection Neurons ◽

Cortical Afferents ◽

Striatal Projection Neurons ◽

Term Potentiation ◽

Frequency Stimulation

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Coding of the long-term value of multiple future rewards in the primate striatum

Journal of Neurophysiology ◽

10.1152/jn.00289.2012 ◽

2013 ◽

Vol 109 (4) ◽

pp. 1140-1151 ◽

Cited By ~ 7

Author(s):

Hiroshi Yamada ◽

Hitoshi Inokawa ◽

Naoyuki Matsumoto ◽

Yasumasa Ueda ◽

Kazuki Enomoto ◽

...

Keyword(s):

Reinforcement Learning ◽

Learning Theories ◽

Projection Neurons ◽

Striatal Neurons ◽

Striatal Projection Neurons ◽

Positive Correlations ◽

Task Trial ◽

The Cost ◽

Near Future

Decisions maximizing benefits involve a tradeoff between the quantity of a reward and the cost of elapsed time until an animal receives it. The estimation of long-term reward values is critical to attain the most desirable outcomes over a certain period of time. Reinforcement learning theories have established algorithms to estimate the long-term reward values of multiple future rewards in which the values of future rewards are discounted as a function of how many steps of choices are necessary to achieve them. Here, we report that presumed striatal projection neurons represent the long-term values of multiple future rewards estimated by a standard reinforcement learning model while monkeys are engaged in a series of trial-and-error choices and adaptive decisions for multiple rewards. We found that the magnitude of activity of a subset of neurons was positively correlated with the long-term reward values, and that of another subset of neurons was negatively correlated throughout the entire decision-making process in individual trials: from the start of the task trial, estimation of the values and their comparison among alternatives, choice execution, and evaluation of the received rewards. An idiosyncratic finding was that neurons showing negative correlations represented reward values in the near future (high discounting), while neurons showing positive correlations represented reward values not only in the near future, but also in the far future (low discounting). These findings provide a new insight that long-term value signals are embedded in two subsets of striatal neurons as high and low discounting of multiple future rewards.

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Beyond Inhibitory Control Training: Inactions and Actions Influence Smartphone App Use Through Changes in Explicit Liking

10.31234/osf.io/nfzr7 ◽

2020 ◽

Author(s):

Niklas Johannes ◽

Moniek Buijzen ◽

Harm Veling

Keyword(s):

Inhibitory Control ◽

Human Behavior ◽

Motor Response ◽

Smartphone App ◽

Smartphone Apps ◽

Substantial Evidence ◽

Motor Responses ◽

Response Training ◽

Influence Behavior

Human behavior can be classified into two basic categories: execution of responses and withholding responses. This classification is used in go/no-go training, where people respond to some objects and withhold their responses to other objects. Despite its simplicity, there is now substantial evidence that such training is powerful in changing human behavior toward such objects. However, it is poorly understood how simple responses can influence behavior. Contrary to the remarkably tenacious idea that go/no-go training changes behavior by strengthening inhibitory control, we propose that the training changes behavior via changes in explicit liking of objects. In two preregistered experiments, we show that go/no-go training influences explicit liking for smartphone apps (Experiment 1 and 2), and that this liking partially mediates the effect of the training on consequential choices for using these apps one day later (Experiment 2). The results highlight the role of evaluations when examining how motor response training influences behavior. This knowledge can inform development of more effective applied motor response training procedures and raises new theoretical questions on the relation between motor responses and affect.

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The role of motor response in feature repetition priming: Encoding of search-relevant information is not contingent on links between features and motor responses.

Journal of Vision ◽

10.1167/12.9.390 ◽

2012 ◽

Vol 12 (9) ◽

pp. 390-390

Author(s):

A. Yashar ◽

T. Makovski ◽

D. Lamy

Keyword(s):

Repetition Priming ◽

Motor Response ◽

Relevant Information ◽

Motor Responses

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Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum

Cells ◽

10.3390/cells11010031 ◽

2021 ◽

Vol 11 (1) ◽

pp. 31

Author(s):

Alicia Rivera ◽

Diana Suárez-Boomgaard ◽

Cristina Miguelez ◽

Alejandra Valderrama-Carvajal ◽

Jérôme Baufreton ◽

...

Keyword(s):

Critical Role ◽

Combined Treatment ◽

Dorsal Striatum ◽

Prolonged Treatment ◽

Projection Neurons ◽

Spine Density ◽

Dopamine D4 Receptor ◽

Striatal Projection Neurons ◽

D4 Receptor

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

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