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Neuron Jan 2022Despite the importance of dopamine for striatal circuit function, mechanistic understanding of dopamine transmission remains incomplete. We recently showed that dopamine...
Despite the importance of dopamine for striatal circuit function, mechanistic understanding of dopamine transmission remains incomplete. We recently showed that dopamine secretion relies on the presynaptic scaffolding protein RIM, indicating that it occurs at active zone-like sites similar to classical synaptic vesicle exocytosis. Here, we establish using a systematic gene knockout approach that Munc13 and Liprin-α, active zone proteins for vesicle priming and release site organization, are important for dopamine secretion. Furthermore, RIM zinc finger and CB domains, which bind to Munc13 and Liprin-α, respectively, are needed to restore dopamine release after RIM ablation. In contrast, and different from typical synapses, the active zone scaffolds RIM-BP and ELKS, and RIM domains that bind to them, are expendable. Hence, dopamine release necessitates priming and release site scaffolding by RIM, Munc13, and Liprin-α, but other active zone proteins are dispensable. Our work establishes that efficient release site architecture mediates fast dopamine exocytosis.
Topics: Corpus Striatum; Dopamine; Exocytosis; Synapses; Synaptic Transmission
PubMed: 34767769
DOI: 10.1016/j.neuron.2021.10.028 -
The Journal of Neuroscience : the... May 2022Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion...
Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition. A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.
Topics: Adult; Dopamine; Dopamine D2 Receptor Antagonists; Emotions; Female; Haloperidol; Humans; Male; Perception
PubMed: 35501156
DOI: 10.1523/JNEUROSCI.2364-21.2022 -
Nature Reviews. Neuroscience Oct 2020Reinforcement learning (RL) is a framework of particular importance to psychology, neuroscience and machine learning. Interactions between these fields, as promoted... (Review)
Review
Reinforcement learning (RL) is a framework of particular importance to psychology, neuroscience and machine learning. Interactions between these fields, as promoted through the common hub of RL, has facilitated paradigm shifts that relate multiple levels of analysis in a singular framework (for example, relating dopamine function to a computationally defined RL signal). Recently, more sophisticated RL algorithms have been proposed to better account for human learning, and in particular its oft-documented reliance on two separable systems: a model-based (MB) system and a model-free (MF) system. However, along with many benefits, this dichotomous lens can distort questions, and may contribute to an unnecessarily narrow perspective on learning and decision-making. Here, we outline some of the consequences that come from overconfidently mapping algorithms, such as MB versus MF RL, with putative cognitive processes. We argue that the field is well positioned to move beyond simplistic dichotomies, and we propose a means of refocusing research questions towards the rich and complex components that comprise learning and decision-making.
Topics: Algorithms; Animals; Brain; Decision Making; Dopamine; Humans; Memory; Models, Neurological; Reinforcement, Psychology; Reward
PubMed: 32873936
DOI: 10.1038/s41583-020-0355-6 -
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 -
International Journal of Molecular... Mar 2023Dopamine has effects on the mammalian heart. These effects can include an increase in the force of contraction, and an elevation of the beating rate and the constriction... (Review)
Review
Dopamine has effects on the mammalian heart. These effects can include an increase in the force of contraction, and an elevation of the beating rate and the constriction of coronary arteries. Depending on the species studied, positive inotropic effects were strong, very modest, or absent, or even negative inotropic effects occurred. We can discern five dopamine receptors. In addition, the signal transduction by dopamine receptors and the regulation of the expression of cardiac dopamine receptors will be of interest to us, because this might be a tempting area of drug development. Dopamine acts in a species-dependent fashion on these cardiac dopamine receptors, but also on cardiac adrenergic receptors. We will discuss the utility of drugs that are currently available as tools to understand cardiac dopamine receptors. The molecule dopamine itself is present in the mammalian heart. Therefore, cardiac dopamine might act as an autocrine or paracrine compound in the mammalian heart. Dopamine itself might cause cardiac diseases. Moreover, the cardiac function of dopamine and the expression of dopamine receptors in the heart can be altered in diseases such as sepsis. Various drugs for cardiac and non-cardiac diseases are currently in the clinic that are, at least in part, agonists or antagonists at dopamine receptors. We define the research needs in order to understand dopamine receptors in the heart better. All in all, an update on the role of dopamine receptors in the human heart appears to be clinically relevant, and is thus presented here.
Topics: Animals; Humans; Dopamine; Heart; Receptors, Adrenergic; Heart Diseases; Receptors, Dopamine; Myocardial Contraction; Mammals
PubMed: 36902474
DOI: 10.3390/ijms24055042 -
Biosensors Jun 2021Neurotransmitters are biochemical molecules that transmit a signal from a neuron across the synapse to a target cell, thus being essential to the function of the central... (Review)
Review
Neurotransmitters are biochemical molecules that transmit a signal from a neuron across the synapse to a target cell, thus being essential to the function of the central and peripheral nervous system. Dopamine is one of the most important catecholamine neurotransmitters since it is involved in many functions of the human central nervous system, including motor control, reward, or reinforcement. It is of utmost importance to quantify the amount of dopamine since abnormal levels can cause a variety of medical and behavioral problems. For instance, Parkinson's disease is partially caused by the death of dopamine-secreting neurons. To date, various methods have been developed to measure dopamine levels, and electrochemical biosensing seems to be the most viable due to its robustness, selectivity, sensitivity, and the possibility to achieve real-time measurements. Even if the electrochemical detection is not facile due to the presence of electroactive interfering species with similar redox potentials in real biological samples, numerous strategies have been employed to resolve this issue. The objective of this paper is to review the materials (metals and metal oxides, carbon materials, polymers) that are frequently used for the electrochemical biosensing of dopamine and point out their respective advantages and drawbacks. Different types of dopamine biosensors, including (micro)electrodes, biosensing platforms, or field-effect transistors, are also described.
Topics: Biosensing Techniques; Carbon; Dopamine; Electrochemical Techniques; Electrodes; Humans; Metals; Neurotransmitter Agents; Oxides; Polymers
PubMed: 34204902
DOI: 10.3390/bios11060179 -
Plant Signaling & Behavior Dec 2020Dopamine (3-hydroxytyramine or 3,4-dihydroxyphenethylamine) has many functions in animals, but also shows several other functions in plants. Since the discovery of... (Review)
Review
Dopamine (3-hydroxytyramine or 3,4-dihydroxyphenethylamine) has many functions in animals, but also shows several other functions in plants. Since the discovery of dopamine in plants in 1968, many studies have provided insight into physiological and biochemical functions, and stress responses of this molecule. In this review, we describe the biosynthesis of dopamine, as well as its role in plant growth and development. In addition, endogenous or exogenously applied dopamine improved the tolerance against several abiotic stresses, such as drought, salt, and nutrient stress. There are also several studies that dopamine contributes to the plant immune response against plant disease. Dopamine affects the expression of many abiotic stresses related genes, which highlights its role as a multi-regulatory molecule and can coordinate many aspects of plant development. Our review emphasized the effects of dopamine against environmental stresses along with future research directions, which will help improve the yield of eco-friendly crops and ensure food security.
Topics: Biosynthetic Pathways; Dopamine; Plant Development; Plants; Stress, Physiological
PubMed: 33040671
DOI: 10.1080/15592324.2020.1827782 -
Chemical Communications (Cambridge,... Dec 2021The rapid and accurate determination of the dopamine (neurotransmitter) and cholesterol level in bio-fluids is significant because they are crucial bioanalytes for... (Review)
Review
The rapid and accurate determination of the dopamine (neurotransmitter) and cholesterol level in bio-fluids is significant because they are crucial bioanalytes for several lethal diseases, which require early diagnosis. The level of DA in the brain is modulated by the dopamine active transporter (DAT), and is influenced by cholesterol levels in the lipid membrane environment. Accordingly, electrochemical biosensors offer rapid and accurate detection and exhibit unique features such as low detection limits even with reduced volumes of analyte, affordability, simple handling, portability and versatility, making them appropriate to deal with augmented challenges in current clinical and point-of-care diagnostics for the determination of dopamine (DA) and cholesterol. This feature article focuses on the development of ultrasensitive electrochemical biosensors for the detection of cholesterol and DA for real-time and onsite applications that can detect targeted analytes with reduced volumes and sub-picomolar concentrations with quick response times. Furthermore, the development of ultrasensitive biosensors cost-effective, simple fabrication procedures, displaying high sensitivity, selectivity, reliability and good stability is significant in the impending era of electrochemical biosensing. Herein, we emphasize on recent advanced nanomaterials used for the ultrasensitive detection of DA and cholesterol and discuss in depth their electrochemical activities towards ultrasensitive responses. Key points describing future perspectives and the challenges during detection with their probable solutions are discussed, and the current market is also surveyed. Further, a comprehensive review of the literature indicates that there is room for improvement in the miniaturization of cholesterol and dopamine biosensors for lab-on-chip devices and overcoming the current technical limitations to facilitate full utilization by patients at home.
Topics: Biosensing Techniques; Cholesterol; Dopamine; Electrochemical Techniques; Humans
PubMed: 34811563
DOI: 10.1039/d1cc05271c -
Proceedings of the National Academy of... May 2023Noninvasive control of neuronal activity in the deep brain can be illuminating for probing brain function and treating dysfunctions. Here, we present a sonogenetic...
Noninvasive control of neuronal activity in the deep brain can be illuminating for probing brain function and treating dysfunctions. Here, we present a sonogenetic approach for controlling distinct mouse behavior with circuit specificity and subsecond temporal resolution. Targeted neurons in subcortical regions were made to express a mutant large conductance mechanosensitive ion channel (MscL-G22S), enabling ultrasound to trigger activity in MscL-expressing neurons in the dorsal striatum and increase locomotion in freely moving mice. Ultrasound stimulation of MscL-expressing neurons in the ventral tegmental area could activate the mesolimbic pathway to trigger dopamine release in the nucleus accumbens and modulate appetitive conditioning. Moreover, sonogenetic stimulation of the subthalamic nuclei of Parkinson's disease model mice improved their motor coordination and mobile time. Neuronal responses to ultrasound pulse trains were rapid, reversible, and repeatable. We also confirmed that the MscL-G22S mutant is more effective to sensitize neurons to ultrasound compared to the wild-type MscL. Altogether, we lay out a sonogenetic approach which can selectively manipulate targeted cells to activate defined neural pathways, affect specific behaviors, and relieve symptoms of neurodegenerative disease.
Topics: Mice; Animals; Neurodegenerative Diseases; Brain; Subthalamic Nucleus; Nucleus Accumbens; Dopamine; Neural Pathways
PubMed: 37216521
DOI: 10.1073/pnas.2220575120 -
Progress in Neuro-psychopharmacology &... Mar 2021There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework... (Review)
Review
There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder. Based on current evidence, we outline an early, preliminary model that links re-experiencing and negative cognitions and mood in PTSD by invoking the interaction between endocannabinoid and dopaminergic signalling in the brain. These interactions between PTSD, dopamine and endocannabinoids may have implications for future therapies for treatment-resistant and comorbid PTSD patients.
Topics: Affect; Animals; Dopamine; Endocannabinoids; Extinction, Psychological; Fear; Humans; Stress Disorders, Post-Traumatic
PubMed: 32991952
DOI: 10.1016/j.pnpbp.2020.110118