Topographic distinction in long-term value signals between presumed dopamine neurons and presumed striatal projection neurons in behaving monkeys

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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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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Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

10.1101/803536 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yan-Feng Zhang ◽

Simon D. Fisher ◽

Manfred Oswald ◽

Jeffery R. Wickens ◽

John N. J. Reynolds

Keyword(s):

Synaptic Plasticity ◽

Reinforcement Learning ◽

Long Term Potentiation ◽

Dopamine Neurons ◽

Projection Neurons ◽

Cholinergic Interneurons ◽

Term Potentiation ◽

Phasic Activation

AbstractPauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1907810116 ◽

2019 ◽

Vol 116 (37) ◽

pp. 18664-18672 ◽

Cited By ~ 4

Author(s):

Goichi Beck ◽

Arun Singh ◽

Jie Zhang ◽

Lisa F. Potts ◽

Jong-Min Woo ◽

...

Keyword(s):

Motor Response ◽

Nonhuman Primates ◽

Firing Frequency ◽

Projection Neurons ◽

Neuronal Responses ◽

Motor Responses ◽

Striatal Projection Neurons ◽

Adaptive Mechanisms

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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A striatal plasticity that supports the long-term preservation of motor function in Parkinsonian mice.

10.1101/2022.01.10.475638 ◽

2022 ◽

Author(s):

Joe C Brague ◽

Rebecca P Seal

Keyword(s):

Dopamine Neurons ◽

Neuron Activity ◽

Motor Deficits ◽

Projection Neurons ◽

Motor Symptoms ◽

Indirect Pathway ◽

Novel Approach ◽

Midbrain Dopamine ◽

Nigrostriatal Dopamine Neurons

Motor deficits of Parkinsons disease (PD) such as rigidity, bradykinesia and akinesia result from a progressive loss of nigrostriatal dopamine neurons. No therapies exist that slow their degeneration and the most effective treatments for the motor symptoms: L-dopa -the precursor to dopamine, and deep brain stimulation can produce dyskinesias and are highly invasive, respectively. Hence, alternative strategies targeted to slow the progression or delay the onset of motor symptoms are still highly sought. Here we report the identification of a long-term striatal plasticity mechanism that delays for several months, the onset of motor deficits in a mouse PD model. Specifically, we show that a one-week transient daily elevation of midbrain dopamine neuron activity during depletion preserves the connectivity of direct but not indirect pathway projection neurons. The findings are consistent with the balance theory of striatal output pathways and suggest a novel approach for treating the motor symptoms of PD.

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