-
Current Opinion in Neurobiology Apr 2013Recent work has advanced our knowledge of phasic dopamine reward prediction error signals. The error signal is bidirectional, reflects well the higher order prediction... (Review)
Review
Recent work has advanced our knowledge of phasic dopamine reward prediction error signals. The error signal is bidirectional, reflects well the higher order prediction error described by temporal difference learning models, is compatible with model-free and model-based reinforcement learning, reports the subjective rather than physical reward value during temporal discounting and reflects subjective stimulus perception rather than physical stimulus aspects. Dopamine activations are primarily driven by reward, and to some extent risk, whereas punishment and salience have only limited activating effects when appropriate controls are respected. The signal is homogeneous in terms of time course but heterogeneous in many other aspects. It is essential for synaptic plasticity and a range of behavioural learning situations.
Topics: Animals; Dopamine; Dopaminergic Neurons; Humans; Models, Neurological; Models, Psychological; Nerve Net; Neuronal Plasticity; Reward; Signal Transduction
PubMed: 23267662
DOI: 10.1016/j.conb.2012.11.012 -
Chemical & Pharmaceutical Bulletin 2016N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N-arachidonoyldopamine...
N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N-arachidonoyldopamine (AADA) and N-oleoyldopamine (ODA) were characterized as transient receptor potential vanilloid type V1 channel (TRPV1) ligands. Recently, it was shown that N-acyldopamines may possess diverse physiological roles in addition to their ligand activities. To study the multiple functions and action mechanisms of endogenous N-acyldopamines, a simple and efficient method of N-acyldopamine synthesis was investigated. The eighteen potentially endogenous N-acyldopamines and two deuterated ones, N-palmitoyl dopamine-d5 and N-stearoyl dopamine-d5, were efficiently synthesized without protective groups in CH2Cl2 under optimized conditions using propylphosphoric acid cyclic anhydride (PPACA) as a condensation agent.
Topics: Dopamine; Molecular Structure; Phosphoric Acids
PubMed: 27373649
DOI: 10.1248/cpb.c16-00162 -
Current Opinion in Neurobiology Apr 2018Phasic dopamine responses demonstrate remarkable simplicity; they code for the differences between received and predicted reward values. Yet this simplicity belies the... (Review)
Review
Phasic dopamine responses demonstrate remarkable simplicity; they code for the differences between received and predicted reward values. Yet this simplicity belies the subtle complexity of the psychological, computational, and contextual factors that influence this signal. Advances in behavioral paradigms and models, in monkeys and rodents, have demonstrated that phasic dopamine responses reflect numerous behavioral computations and factors including choice, subjective value, confidence, and context. The application of optogenetics has provided evidence that dopamine reward prediction error responses cause value learning. Furthermore, studies using advanced circuit tracing techniques have begun to uncover the biological network implementation of the reward learning algorithm. The purpose of this review is to summarize the recent advances in dopamine neurophysiology and synthesize an updated account of the behavioral function of dopamine signals.
Topics: Animals; Brain; Choice Behavior; Dopamine; Dopaminergic Neurons; Humans; Optogenetics; Reward
PubMed: 29505948
DOI: 10.1016/j.conb.2018.02.005 -
PLoS Computational Biology Mar 2021Slow-timescale (tonic) changes in dopamine (DA) contribute to a wide variety of processes in reinforcement learning, interval timing, and other domains. Furthermore,...
Slow-timescale (tonic) changes in dopamine (DA) contribute to a wide variety of processes in reinforcement learning, interval timing, and other domains. Furthermore, changes in tonic DA exert distinct effects depending on when they occur (e.g., during learning vs. performance) and what task the subject is performing (e.g., operant vs. classical conditioning). Two influential theories of tonic DA-the average reward theory and the Bayesian theory in which DA controls precision-have each been successful at explaining a subset of empirical findings. But how the same DA signal performs two seemingly distinct functions without creating crosstalk is not well understood. Here we reconcile the two theories under the unifying framework of 'rational inattention,' which (1) conceptually links average reward and precision, (2) outlines how DA manipulations affect this relationship, and in so doing, (3) captures new empirical phenomena. In brief, rational inattention asserts that agents can increase their precision in a task (and thus improve their performance) by paying a cognitive cost. Crucially, whether this cost is worth paying depends on average reward availability, reported by DA. The monotonic relationship between average reward and precision means that the DA signal contains the information necessary to retrieve the precision. When this information is needed after the task is performed, as presumed by Bayesian inference, acute manipulations of DA will bias behavior in predictable ways. We show how this framework reconciles a remarkably large collection of experimental findings. In reinforcement learning, the rational inattention framework predicts that learning from positive and negative feedback should be enhanced in high and low DA states, respectively, and that DA should tip the exploration-exploitation balance toward exploitation. In interval timing, this framework predicts that DA should increase the speed of the internal clock and decrease the extent of interference by other temporal stimuli during temporal reproduction (the central tendency effect). Finally, rational inattention makes the new predictions that these effects should be critically dependent on the controllability of rewards, that post-reward delays in intertemporal choice tasks should be underestimated, and that average reward manipulations should affect the speed of the clock-thus capturing empirical findings that are unexplained by either theory alone. Our results suggest that a common computational repertoire may underlie the seemingly heterogeneous roles of DA.
Topics: Attention; Bayes Theorem; Cognition; Computational Biology; Dopamine; Humans; Models, Neurological; Reinforcement, Psychology
PubMed: 33760806
DOI: 10.1371/journal.pcbi.1008659 -
Genes, Brain, and Behavior Jan 2016The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the... (Review)
Review
The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study.
Topics: Animals; Behavior; Dopamine; Humans; Mesencephalon; Mutation; Neurogenesis
PubMed: 26548362
DOI: 10.1111/gbb.12257 -
Oxidative Medicine and Cellular... 2016Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has... (Review)
Review
Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has been implicated in different nervous system diseases. The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. The role of dopamine dysfunction as a consequence of oxidative stress is involved in health and disease. Introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the therapeutic potential of antioxidant compounds as a coadjuvant treatment to conventional neurological disorders is discussed.
Topics: Animals; Antidepressive Agents; Dopamine; Endocrine System; Humans; Neuroprotective Agents; Oxidative Stress; Receptors, Dopamine
PubMed: 26770661
DOI: 10.1155/2016/9730467 -
Schizophrenia Research Jul 2023The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter...
BACKGROUND
The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter in patients is still missing. The present study assessed dopamine and related metabolites in the cerebrospinal fluid (CSF) of first-episode psychosis (FEP) subjects.
METHODS
Forty first-episode psychosis subjects and twenty healthy age-matched volunteers were recruited via the Karolinska Schizophrenia Project, a multidisciplinary research consortium that investigates the pathophysiology of schizophrenia. Psychopathology, disease severity, and cognitive performance were rated as well as cerebrospinal fluid concentrations of dopamine and related metabolites were measured using a sensitive high-pressure liquid chromatography assay.
RESULTS
CSF dopamine was reliably detected in 50 % of healthy controls and in 65 % of first-episode psychosis subjects and significantly higher in first-episode psychosis subjects compared to age-matched healthy controls. No difference in CSF dopamine levels was observed between drug-naive subjects and subjects with short exposure to antipsychotics. The dopamine concentrations were positively associated with illness severity and deficits in executive functioning.
CONCLUSIONS
Dopamine dysfunction has long been considered a cornerstone of the pathophysiology of schizophrenia, although biochemical support for elevated brain dopamine levels has been lacking. The results of the present study, showing that FEP subjects have increased CSF dopamine levels that correlate to disease symptoms, should fill the knowledge gap in this regard.
Topics: Humans; Dopamine; Psychotic Disorders; Schizophrenia; Brain; Cognition
PubMed: 37271040
DOI: 10.1016/j.schres.2023.05.012 -
Cell Chemical Biology Jun 2021Dopamine is a modulatory neurotransmitter involved in learning, motor functions, and reward. Many neuropsychiatric disorders, including Parkinson's disease, autism, and... (Review)
Review
Dopamine is a modulatory neurotransmitter involved in learning, motor functions, and reward. Many neuropsychiatric disorders, including Parkinson's disease, autism, and schizophrenia, are associated with imbalances or dysfunction in the dopaminergic system. Yet, our understanding of these pervasive public health issues is limited by our ability to effectively image dopamine in humans, which has long been a goal for chemists and neuroscientists. The last two decades have witnessed the development of many molecules used to trace dopamine. We review the small molecules, nanoparticles, and protein sensors used with fluorescent microscopy/photometry, MRI, and PET that shape dopamine research today. None of these tools observe dopamine itself, but instead harness the biology of the dopamine system-its synthetic and metabolic pathways, synaptic vesicle cycle, and receptors-in elegant ways. Their advantages and weaknesses are covered here, along with recent examples and the chemistry and biology that allow them to function.
Topics: Dopamine; Humans; Parkinson Disease
PubMed: 33894160
DOI: 10.1016/j.chembiol.2021.04.005 -
Cell Reports Oct 2022Goal-directed navigation requires learning to accurately estimate location and select optimal actions in each location. Midbrain dopamine neurons are involved in reward...
Goal-directed navigation requires learning to accurately estimate location and select optimal actions in each location. Midbrain dopamine neurons are involved in reward value learning and have been linked to reward location learning. They are therefore ideally placed to provide teaching signals for goal-directed navigation. By imaging dopamine neural activity as mice learned to actively navigate a closed-loop virtual reality corridor to obtain reward, we observe phasic and pre-reward ramping dopamine activity, which are modulated by learning stage and task engagement. A Q-learning model incorporating position inference recapitulates our results, displaying prediction errors resembling phasic and ramping dopamine neural activity. The model predicts that ramping is followed by improved task performance, which we confirm in our experimental data, indicating that the dopamine ramp may have a teaching effect. Our results suggest that midbrain dopamine neurons encode phasic and ramping reward prediction error signals to improve goal-directed navigation.
Topics: Animals; Dopamine; Dopaminergic Neurons; Goals; Mesencephalon; Mice; Reward
PubMed: 36223748
DOI: 10.1016/j.celrep.2022.111470 -
Journal of Neurochemistry Jun 2014The molecular mechanisms causing the loss of dopaminergic neurons containing neuromelanin in the substantia nigra and responsible for motor symptoms of Parkinson's... (Review)
Review
The molecular mechanisms causing the loss of dopaminergic neurons containing neuromelanin in the substantia nigra and responsible for motor symptoms of Parkinson's disease are still unknown. The discovery of genes associated with Parkinson's disease (such as alpha synuclein (SNCA), E3 ubiquitin protein ligase (parkin), DJ-1 (PARK7), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL-1), serine/threonine-protein kinase (PINK-1), leucine-rich repeat kinase 2 (LRRK2), cation-transporting ATPase 13A1 (ATP13A), etc.) contributed enormously to basic research towards understanding the role of these proteins in the sporadic form of the disease. However, it is generally accepted by the scientific community that mitochondria dysfunction, alpha synuclein aggregation, dysfunction of protein degradation, oxidative stress and neuroinflammation are involved in neurodegeneration. Dopamine oxidation seems to be a complex pathway in which dopamine o-quinone, aminochrome and 5,6-indolequinone are formed. However, both dopamine o-quinone and 5,6-indolequinone are so unstable that is difficult to study and separate their roles in the degenerative process occurring in Parkinson's disease. Dopamine oxidation to dopamine o-quinone, aminochrome and 5,6-indolequinone seems to play an important role in the neurodegenerative processes of Parkinson's disease as aminochrome induces: (i) mitochondria dysfunction, (ii) formation and stabilization of neurotoxic protofibrils of alpha synuclein, (iii) protein degradation dysfunction of both proteasomal and lysosomal systems and (iv) oxidative stress. The neurotoxic effects of aminochrome in dopaminergic neurons can be inhibited by: (i) preventing dopamine oxidation of the transporter that takes up dopamine into monoaminergic vesicles with low pH and dopamine oxidative deamination catalyzed by monoamino oxidase (ii) dopamine o-quinone, aminochrome and 5,6-indolequinone polymerization to neuromelanin and (iii) two-electron reduction of aminochrome catalyzed by DT-diaphorase. Furthermore, dopamine conversion to NM seems to have a dual role, protective and toxic, depending mostly on the cellular context. Dopamine oxidation to dopamine o-quinone, aminochrome and 5,6-indolequinone plays an important role in neurodegeneration in Parkinson's disease since they induce mitochondria and protein degradation dysfunction; formation of neurotoxic alpha synuclein protofibrils and oxidative stress. However, the cells have a protective system against dopamine oxidation composed by dopamine uptake mediated by Vesicular monoaminergic transporter-2 (VMAT-2), neuromelanin formation, two-electron reduction and GSH-conjugation mediated by Glutathione S-transferase M2-2 (GSTM2).
Topics: Animals; Dopamine; Glutathione; Humans; Indolequinones; Melanins; Monoamine Oxidase; Parkinson Disease; Quinones
PubMed: 24548101
DOI: 10.1111/jnc.12686