ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Three mechanisms by which striatal denervation causes breakdown of dopamine signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Striatal Dopamine Actions and Movement: Inferences from Parkinson Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Striatal synaptic adaptations in Parkinson's disease.Neurobiology of disease · 2022Review
- A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning.Frontiers in computational neuroscience · 2022Article
- An integrative model of Parkinson's disease treatment including levodopa pharmacokinetics, dopamine kinetics, basal ganglia neurotransmission and motor action throughout disease progression.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Abundance Compensates Kinetics: Similar Effect of Dopamine Signals on D1 and D2 Receptor Populations.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Insights into Parkinson's disease from computational models of the basal ganglia.Journal of neurology, neurosurgery, and psychiatry · 2018Review
- Striatal neurons get a kick out of dopamine.The Journal of physiology · 2017Article
- Dopamine Manipulation Affects Response Vigor Independently of Opportunity Cost.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.Molecular neurobiology · 2016Article
- Loss of Homeostasis in the Direct Pathway in a Mouse Model of Asymptomatic Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- How compensation breaks down in Parkinson's disease: Insights from modeling of denervated striatum.Movement disorders : official journal of the Movement Disorder Society · 2016Review
- Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Novel Pattern of Iron Deposition in the Fascicula Nigrale in Patients with Parkinson's Disease: A Pilot Study.Radiology research and practice · 2016Article
- Modeling falls in Parkinson's disease: Slow gait, freezing episodes and falls in rats with extensive striatal dopamine loss.Behavioural brain research · 2015Article
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive loss of nigrostriatal dopamine (DA) neurons is the neuropathological hallmark of Parkinson's disease (PD). Symptoms of the disease can often be treated by DA D2 agonists and thus seem related to disinhibition of the indirect striatal pathway. However, there is no evidence that symptoms arise by low extracellular DA concentration or are associated with reduced D2 receptor binding. Here I provide a theoretical analysis of the pathophysiology and postsynaptic adaptation resulting from striatal DA denervation. I found that progressive denervation may alter DA signaling by three independent mechanisms depending on degree of denervation and macroscopic morphology of the lesion. As long as the remaining innervation stays anatomically coherent, denervation reduces phasic variations in extracellular DA, but the DA tone is not changed. The reduction of phasic signaling can be partially compensated by upregulating postsynaptic signaling cascades. However, changes in DA dynamics evade compensation. With 80-99% denervation, a persistent aberrant signal develops in D2-regulated pathways caused by random fluctuations in tonic DA release. Permanent low DA levels occur in regions completely void of innervation. Simulation of l-dopa therapy reduced the aberrant D2 signal. With a high degree of denervation, l-dopa enhanced another aberrant signal, this time in the D1 pathway. This analysis provides a quantitative, physiologically consistent view of the early and late stages of PD, the effect of main therapeutic medications, and potential side effects. The mechanisms described here may also provide an explanation to currently inexplicable pathological phenomena such as psycho stimulant-induced contraversive rotations in animal models.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.