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Journal of Neuroscience Research Dec 2019Play is an important part of normal childhood development and can be readily studied in the laboratory rat in the form of rough-and-tumble play. Given the robust nature... (Review)
Review
Play is an important part of normal childhood development and can be readily studied in the laboratory rat in the form of rough-and-tumble play. Given the robust nature of rough-and-tumble play, it has often been assumed that the basal ganglia would have a prominent role in modulating this behavior. Recent work using c-fos expression as a metabolic marker for neural activity combined with temporary inactivation of relevant corticostriatal regions and pharmacological manipulations of opioid, cannabinoid, and dopamine systems has led to a better understanding of how basal ganglia circuitry may be involved in modulating social play in the juvenile rat. Studies using selective play deprivation have also provided insight into the consequences of playful experiences on basal ganglia function. Data reviewed in this paper support a role for the basal ganglia in social play and also suggest that corticostriatal functioning also benefits from playful activities.
Topics: Animals; Basal Ganglia; Behavior, Animal; Dopamine; Play and Playthings; Rats; Species Specificity
PubMed: 31165503
DOI: 10.1002/jnr.24475 -
Macromolecular Bioscience Mar 2023Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the...
Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.
Topics: Humans; Dopamine; Cell Survival; Neuroblastoma; Drug Delivery Systems; Polymers
PubMed: 36592964
DOI: 10.1002/mabi.202200397 -
Philosophical Transactions of the Royal... Aug 2022The role of oxytocin in maternal caregiving and other postpartum behaviours has been studied for more than five decades. How oxytocin interacts with other neurochemical... (Review)
Review
The role of oxytocin in maternal caregiving and other postpartum behaviours has been studied for more than five decades. How oxytocin interacts with other neurochemical systems to enact these behavioural changes, however, is only slowly being elucidated. The best-studied oxytocin-neurotransmitter interaction is with the mesolimbic dopamine system, and this interaction is essential for maternal motivation and active caregiving behaviours such as retrieval of pups. Considerably less attention has been dedicated to investigating how oxytocin interacts with central serotonin to influence postpartum behaviour. Recently, it has become clear that while oxytocin-dopamine interactions regulate the motivational and pup-approach aspects of maternal caregiving behaviours, oxytocin-serotonin interactions appear to regulate nearly all other aspects including postpartum nursing, aggression, anxiety-like behaviour and stress coping strategy. Collectively, oxytocin's interactions with central dopamine and serotonin systems are thus critical for the entire suite of behavioural adaptations exhibited in the postpartum period, and these sites of interaction are potential pharmacological targets for where oxytocin could help to ameliorate deficits in maternal caregiving and poor postpartum mental health. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.
Topics: Dopamine; Female; Humans; Maternal Behavior; Oxytocin; Postpartum Period; Serotonin
PubMed: 35858105
DOI: 10.1098/rstb.2021.0062 -
Nature Neuroscience Apr 2021Dopamine prediction error responses are essential components of universal learning mechanisms. However, it is unknown whether individual dopamine neurons reflect the...
Dopamine prediction error responses are essential components of universal learning mechanisms. However, it is unknown whether individual dopamine neurons reflect the shape of reward distributions. Here, we used symmetrical distributions with differently weighted tails to investigate how the frequency of rewards and reward prediction errors influence dopamine signals. Rare rewards amplified dopamine responses, even when conventional prediction errors were identical, indicating a mechanism for learning the complexities of real-world incentives.
Topics: Animals; Brain; Dopamine; Dopaminergic Neurons; Learning; Macaca mulatta; Male; Reinforcement, Psychology; Reward
PubMed: 33686298
DOI: 10.1038/s41593-021-00807-7 -
Communications Biology Jun 2022Dopamine supports locomotor control and higher brain functions such as motivation and learning. Consistently, dopaminergic dysfunction is involved in a spectrum of...
Dopamine supports locomotor control and higher brain functions such as motivation and learning. Consistently, dopaminergic dysfunction is involved in a spectrum of neurological and neuropsychiatric diseases. Detailed data on dopamine dynamics is needed to understand how dopamine signals translate into cellular and behavioral responses, and to uncover pathological disturbances in dopamine-related diseases. Genetically encoded fluorescent dopamine sensors have recently enabled unprecedented monitoring of dopamine dynamics in vivo. However, these sensors' utility for in vitro and ex vivo assays remains unexplored. Here, we present a blueprint for making dopamine sniffer cells for multimodal dopamine detection. We generated sniffer cell lines with inducible expression of seven different dopamine sensors and perform a head-to-head comparison of sensor properties to guide users in sensor selection. In proof-of-principle experiments, we apply the sniffer cells to record endogenous dopamine release from cultured neurons and striatal slices, and for determining tissue dopamine content. Furthermore, we use the sniffer cells to measure dopamine uptake and release via the dopamine transporter as a radiotracer free, high-throughput alternative to electrochemical- and radiotracer-based assays. Importantly, the sniffer cell framework can readily be applied to the growing list of genetically encoded fluorescent neurotransmitter sensors.
Topics: Corpus Striatum; Dopamine; Learning; Neurons; Neurotransmitter Agents
PubMed: 35689020
DOI: 10.1038/s42003-022-03488-5 -
ACS Applied Materials & Interfaces Mar 2021Oligonucleotide receptors (aptamers), which change conformation upon target recognition, enable electronic biosensing under high ionic-strength conditions when coupled...
Oligonucleotide receptors (aptamers), which change conformation upon target recognition, enable electronic biosensing under high ionic-strength conditions when coupled to field-effect transistors (FETs). Because highly negatively charged aptamer backbones are influenced by ion content and concentration, biosensor performance and target sensitivities were evaluated under application conditions. For a recently identified dopamine aptamer, physiological concentrations of Mg and Ca in artificial cerebrospinal fluid produced marked potentiation of dopamine FET-sensor responses. By comparison, divalent cation-associated signal amplification was not observed for FET sensors functionalized with a recently identified serotonin aptamer or a previously reported dopamine aptamer. Circular dichroism spectroscopy revealed Mg- and Ca-induced changes in target-associated secondary structure for the new dopamine aptamer, but not the serotonin aptamer nor the old dopamine aptamer. Thioflavin T displacement corroborated the Mg dependence of the new dopamine aptamer for target detection. These findings imply allosteric binding interactions between divalent cations and dopamine for the new dopamine aptamer. Developing and testing sensors in ionic environments that reflect intended applications are best practices for identifying aptamer candidates with favorable attributes and elucidating sensing mechanisms.
Topics: Aptamers, Nucleotide; Benzothiazoles; Biosensing Techniques; Calcium; Dopamine; Electrochemical Techniques; G-Quadruplexes; Magnesium; Serotonin; Transistors, Electronic
PubMed: 33410656
DOI: 10.1021/acsami.0c17535 -
ELife Oct 2023Dopamine system dysfunction is implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive...
Dopamine system dysfunction is implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive symptoms remain unresponsive and novel paradigms investigating the circuit substrates underlying cognitive deficits are critically needed. The frontal cortex and its dopaminergic input from the midbrain are implicated in cognitive functions and undergo maturational changes during adolescence. Here, we used mice carrying mutations in or to model mesofrontal dopamine circuit deficiencies and test circuit-based neurostimulation strategies to restore cognitive functions. We found that in a memory-guided spatial navigation task, frontal cortical neurons were activated coordinately at the decision-making point in wild-type but not -/- mice. Chemogenetic stimulation of midbrain dopamine neurons or optogenetic stimulation of frontal cortical dopamine axons in a limited adolescent period consistently reversed genetic defects in mesofrontal innervation, task-coordinated neuronal activity, and memory-guided decision-making at adulthood. Furthermore, adolescent stimulation of dopamine neurons also reversed the same cognitive deficits in +/- mice. Our findings reveal common mesofrontal circuit alterations underlying the cognitive deficits caused by two different genes and demonstrate the feasibility of adolescent neurostimulation to reverse these circuit and behavioral deficits. These results may suggest developmental windows and circuit targets for treating cognitive deficits in neurodevelopmental disorders.
Topics: Animals; Mice; Dopamine; Frontal Lobe; Cognition; Antipsychotic Agents; Prefrontal Cortex; Nerve Tissue Proteins
PubMed: 37830916
DOI: 10.7554/eLife.87414 -
Frontiers in Neural Circuits 2021Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by altered social interaction and communication, and repetitive, restricted, inflexible... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by altered social interaction and communication, and repetitive, restricted, inflexible behaviors. Approximately 1.5-2% of the general population meet the diagnostic criteria for ASD and several brain regions including the cortex, amygdala, cerebellum and basal ganglia have been implicated in ASD pathophysiology. The midbrain dopamine system is an important modulator of cellular and synaptic function in multiple ASD-implicated brain regions via anatomically and functionally distinct dopaminergic projections. The dopamine hypothesis of ASD postulates that dysregulation of dopaminergic projection pathways could contribute to the behavioral manifestations of ASD, including altered reward value of social stimuli, changes in sensorimotor processing, and motor stereotypies. In this review, we examine the support for the idea that cell-autonomous changes in dopaminergic function are a core component of ASD pathophysiology. We discuss the human literature supporting the involvement of altered dopamine signaling in ASD including genetic, brain imaging and pharmacologic studies. We then focus on genetic mouse models of syndromic neurodevelopmental disorders in which single gene mutations lead to increased risk for ASD. We highlight studies that have directly examined dopamine neuron number, morphology, physiology, or output in these models. Overall, we find considerable support for the idea that the dopamine system may be dysregulated in syndromic ASDs; however, there does not appear to be a consistent signature and some models show increased dopaminergic function, while others have deficient dopamine signaling. We conclude that dopamine dysregulation is common in syndromic forms of ASD but that the specific changes may be unique to each genetic disorder and may not account for the full spectrum of ASD-related manifestations.
Topics: Animals; Autism Spectrum Disorder; Brain; Dopamine; Dopaminergic Neurons; Humans; Mice; Mice, Transgenic; Mutation
PubMed: 34366796
DOI: 10.3389/fncir.2021.700968 -
Journal of Cellular Physiology May 2020Dopamine (DA) is produced from tyrosine by tyrosine hydroxylase (TH). A recent study has reported that DA promotes the mineralization of murine preosteoblasts. However,...
Dopamine (DA) is produced from tyrosine by tyrosine hydroxylase (TH). A recent study has reported that DA promotes the mineralization of murine preosteoblasts. However, the role of DA in odontoblasts has not been examined. Therefore, in this investigation, we researched the expression of TH and DA in odontoblasts and the effects of DA on the differentiation of preodontoblasts (KN-3 cells). Immunostaining showed that TH and DA were intensely expressed in odontoblasts and preodontoblasts of rat incisors and molars. KN-3 cells expressed D1-like and D2-like receptors for DA. Furthermore, DA promoted odontoblastic differentiation of KN-3 cells, whereas an antagonist of D1-like receptors and a PKA signaling blocker, inhibited such differentiation. However, antagonists of D2-like receptors promoted differentiation. These results suggested that DA in preodontoblasts and odontoblasts might promote odontoblastic differentiation through D1-like receptors, but not D2-like receptors, and PKA signaling in an autocrine or paracrine manner and plays roles in dentinogenesis.
Topics: Animals; Cell Differentiation; Cell Line; Dental Pulp; Dopamine; Gene Expression Regulation; Male; Odontoblasts; Rats; Rats, Sprague-Dawley
PubMed: 31612496
DOI: 10.1002/jcp.29314 -
Neurobiology of Learning and Memory Jul 2023Excitatory pyramidal (PYR) cell activation of interneurons (INT) produces network oscillations that underlie cognitive processes in the hippocampus (CA1). Neural...
Excitatory pyramidal (PYR) cell activation of interneurons (INT) produces network oscillations that underlie cognitive processes in the hippocampus (CA1). Neural projections from the ventral tegmental area (VTA) to the hippocampus contribute to novelty detection by modulating CA1 PYR and INT activity. The role of the VTA in the VTA-hippocampus loop is mostly attributed to the dopamine neurons although the VTA glutamate-releasing terminals are dominant in the hippocampus. Because of the traditional focus on VTA dopamine circuits, how VTA glutamate inputs modulate PYR activation of INT in CA1 neuronal ensembles is poorly understood and has not been distinguished from the VTA dopamine inputs. By combining CA1 extracellular recording with VTA photostimulation in anesthetized mice, we compared the effects of VTA dopamine and glutamate input on CA1 PYR/INT connections. Stimulation of VTA glutamate neurons shortened PYR/INT connection time without altering the synchronization or connectivity strength. Conversely, activation of VTA dopamine inputs delayed CA1 PYR/INT connection time and increased the synchronization in putative pairs. Taken together, we conclude that VTA dopamine and glutamate projections produce tract-specific effects on CA1 PYR/INT connectivity and synchrony. As such, selective activation or co-activation of these systems will likely produce a range of modulatory effects on local CA1 circuits.
Topics: Mice; Animals; Dopamine; Ventral Tegmental Area; Hippocampus; Glutamic Acid; Dopaminergic Neurons
PubMed: 37119849
DOI: 10.1016/j.nlm.2023.107760