scholarly journals Cross-hemispheric dopamine projections have functional significance

2016 ◽  
Vol 113 (25) ◽  
pp. 6985-6990 ◽  
Author(s):  
Megan E. Fox ◽  
Maria A. Mikhailova ◽  
Caroline E. Bass ◽  
Pavel Takmakov ◽  
Raul R. Gainetdinov ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Ventral Striatum ◽  
Dopamine Neurons ◽  
Dopamine System ◽  
Anesthetized Rats ◽  
Freely Moving ◽  
Midbrain Dopamine ◽  
Dopamine Signaling ◽  
6 Hydroxydopamine ◽  
Stimulation Of

Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson’s disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine–lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.

scholarly journals Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats

2021 ◽  
pp. 1-24
Author(s):  
Juho-Matti Renko ◽  
Arun Kumar Mahato ◽  
Tanel Visnapuu ◽  
Konsta Valkonen ◽  
Mati Karelson ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Wild Type ◽  
Disease Modifying Therapy ◽  
Immortalized Cells ◽  
Midbrain Dopamine ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurological disorder where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor symptoms. Currently, no treatment is able to halt the progression of PD. Glial cell line-derived neurotrophic factor (GDNF) rescues degenerating dopamine neurons both in vitro and in animal models of PD. When tested in PD patients, however, the outcomes from intracranial GDNF infusion paradigms have been inconclusive, mainly due to poor pharmacokinetic properties. Objective: We have developed drug-like small molecules, named BT compounds that activate signaling through GDNF’s receptor, the transmembrane receptor tyrosine kinase RET, both in vitro and in vivo and are able to penetrate through the blood-brain barrier. Here we evaluated the properties of BT44, a second generation RET agonist, in immortalized cells, dopamine neurons and rat 6-hydroxydopamine model of PD. Methods: We used biochemical, immunohistochemical and behavioral methods to evaluate the effects of BT44 on dopamine system in vitro and in vivo. Results: BT44 selectively activated RET and intracellular pro-survival AKT and MAPK signaling pathways in immortalized cells. In primary midbrain dopamine neurons cultured in serum-deprived conditions, BT44 promoted the survival of the neurons derived from wild-type, but not from RET knockout mice. BT44 also protected cultured wild-type dopamine neurons from MPP +-induced toxicity. In a rat 6-hydroxydopamine model of PD, BT44 reduced motor imbalance and could have protected dopaminergic fibers in the striatum. Conclusion: BT44 holds potential for further development into a novel, possibly disease-modifying therapy for PD.

Stimulation of the nigrostriatal dopamine system produces hypertension and tachycardia in rats

1994 ◽  
Vol 266 (6) ◽  
pp. H2489-H2496 ◽  
Author(s):  
M. T. Lin ◽  
J. J. Yang
Keyword(s):  
Corpus Striatum ◽  
Substantia Nigra Pars Compacta ◽  
Dopamine System ◽  
Arterial Blood ◽  
Nigrostriatal Dopamine ◽  
Induced Hypertension ◽  
Bilateral Vagotomy ◽  
6 Hydroxydopamine ◽  
Da Release ◽  
Stimulation Of

To test for the ability of the nigrostriatal dopamine (DA) system to influence cardiovascular function, experiments were carried out to assess the effects of electrical or chemical stimulation of the nigrostriatal DA system on arterial blood pressure, heart rate, and striatal DA release in anesthetized rats. Electrical stimulation of the substantia nigra pars compacta (SNC), in addition to enhancing the DA release in the corpus striatum (CS), elicited proportional hypertension and tachycardia. This could be mimicked by microinjection of two excitatory amino acids, kainic acid and glutamate, into the SNC area of rat brain. The SNC stimulation-induced hypertension, tachycardia, and increased striatal DA release were attenuated by prior destruction of the nigrostriatal DA system produced by intramedial forebrain bundle injection of 6-hydroxydopamine and by prior blockade of postsynaptic DA receptors produced by intra-CS injection of DA receptor antagonists, haloperidol or pimozide. The SNC stimulation-induced hypertension was attenuated by spinal transection, whereas the SNC stimulation-induced tachycardia was attenuated by bilateral vagotomy. The data suggest that stimulation of the nigrostriatal DA system produces both hypertension and tachycardia in rats.

scholarly journals Midbrain dopamine neurons signal aversion in a reward-context-dependent manner

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Hideyuki Matsumoto ◽  
Ju Tian ◽  
Naoshige Uchida ◽  
Mitsuko Watabe-Uchida
Keyword(s):  
Dopamine Neurons ◽  
Prediction Errors ◽  
Dependent Manner ◽  
Value Prediction ◽  
Signal Value ◽  
Aversive Events ◽  
High Reward ◽  
Midbrain Dopamine ◽  
Dopamine Signaling ◽  
Reward And Punishment

Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons’ responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons’ responses to that odor reflected the integrated value of both outcomes. Thus, in low reward contexts, dopamine neurons signal value prediction errors (VPEs) integrating information about both reward and aversion in a common currency. In contrast, in high reward contexts, dopamine neurons acquired a short-latency excitation to aversive events that masked their VPE signaling. Our results demonstrate the importance of considering the contexts to examine the representation in dopamine neurons and uncover different modes of dopamine signaling, each of which may be adaptive for different environments.

scholarly journals Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

2015 ◽  
Vol 114 (2) ◽  
pp. 1072-1082 ◽  
Author(s):  
Aaron G. Roseberry
Keyword(s):  
Ventral Tegmental Area ◽  
Food Restriction ◽  
Dopamine Release ◽  
Dopamine Neurons ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Axon Terminals ◽  
Highly Active ◽  
Target Sites ◽  
Ventral Tegmental

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active.

scholarly journals BOLD and its connection to dopamine release in human striatum: a cross-cohort comparison

2016 ◽  
Vol 371 (1705) ◽  
pp. 20150352 ◽  
Author(s):  
Terry Lohrenz ◽  
Kenneth T. Kishida ◽  
P. Read Montague
Keyword(s):  
Prediction Error ◽  
Dopamine Release ◽  
Computational Models ◽  
Dopamine Neurons ◽  
Clear Correlation ◽  
Bold Signal ◽  
Fast Scan Cyclic Voltammetry ◽  
Related Information ◽  
Midbrain Dopamine ◽  
The Relationship

Activity in midbrain dopamine neurons modulates the release of dopamine in terminal structures including the striatum, and controls reward-dependent valuation and choice. This fluctuating release of dopamine is thought to encode reward prediction error (RPE) signals and other value-related information crucial to decision-making, and such models have been used to track prediction error signals in the striatum as encoded by BOLD signals. However, until recently there have been no comparisons of BOLD responses and dopamine responses except for one clear correlation of these two signals in rodents. No such comparisons have been made in humans. Here, we report on the connection between the RPE-related BOLD signal recorded in one group of subjects carrying out an investment task, and the corresponding dopamine signal recorded directly using fast-scan cyclic voltammetry in a separate group of Parkinson's disease patients undergoing DBS surgery while performing the same task. The data display some correspondence between the signal types; however, there is not a one-to-one relationship. Further work is necessary to quantify the relationship between dopamine release, the BOLD signal and the computational models that have guided our understanding of both at the level of the striatum. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.

Selective Inhibition by Adenosine of mGluR IPSPs in Dopamine Neurons After Cocaine Treatment

2000 ◽  
Vol 83 (3) ◽  
pp. 1307-1314 ◽  
Author(s):  
Christopher D. Fiorillo ◽  
John T. Williams
Keyword(s):  
Dopamine Release ◽  
Metabotropic Glutamate Receptor ◽  
Selective Inhibition ◽  
Dopamine Neurons ◽  
Dopamine System ◽  
Extracellular Adenosine ◽  
Mesolimbic Dopamine System ◽  
Metabotropic Glutamate ◽  
Postsynaptic Potential ◽  
A1 Receptor

With repeated exposure to psychostimulants such as cocaine and amphetamine, long-lasting changes occur in the mesolimbic dopamine system that are thought to underlie continued drug-seeking and relapse. One consequence of repeated cocaine treatment is an increase in extracellular adenosine in the ventral tegmental area (VTA), which results in tonic inhibition of synaptic input to dopamine neurons. The synapse specificity of this increased adenosine tone was examined on glutamate- and GABA-mediated responses using the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The slow, metabotropic glutamate receptor (mGluR)-mediated inhibitory postsynaptic potential (IPSP) was enhanced by DPCPX only in slices from psychostimulant-treated animals. Under resting conditions, DPCPX was without effect on fast excitatory postsynaptic currents (EPSCs) in slices from saline- or cocaine-treated animals. However, in the presence of amphetamine, DPCPX did augment fast EPSCs in slices from cocaine-treated rats. Although DPCPX increased GABAB IPSPs, the magnitude of the increase was not altered by cocaine pretreatment, even in the presence of amphetamine. This suggests that the elevated adenosine tone induced by cocaine treatment acts preferentially on glutamate terminals. Furthermore, the inhibition of the mGluR IPSP by endogenous adenosine may result in more effective burst firing mediated by glutamate afferents in cocaine-treated rats, a phenomenon known to enhance dopamine release.

scholarly journals Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms

2017 ◽  
Vol 115 (1) ◽  
pp. 198-203 ◽  
Author(s):  
Daniela Radl ◽  
Martina Chiacchiaretta ◽  
Robert G. Lewis ◽  
Karen Brami-Cherrier ◽  
Ludovico Arcuri ◽  
...  
Keyword(s):  
Motor Activity ◽  
Cellular Response ◽  
Motor Behavior ◽  
Dopamine D2 Receptor ◽  
Cellular Responses ◽  
Dopamine Neurons ◽  
Dopamine Synthesis ◽  
Striatal Neurons ◽  
Dopamine System ◽  
Dopamine Signaling

The dopamine D2 receptor (D2R) is a major component of the dopamine system. D2R-mediated signaling in dopamine neurons is involved in the presynaptic regulation of dopamine levels. Postsynaptically, i.e., in striatal neurons, D2R signaling controls complex functions such as motor activity through regulation of cell firing and heterologous neurotransmitter release. The presence of two isoforms, D2L and D2S, which are generated by a mechanism of alternative splicing of the Drd2 gene, raises the question of whether both isoforms may equally control presynaptic and postsynaptic events. Here, we addressed this question by comparing behavioral and cellular responses of mice with the selective ablation of either D2L or D2S isoform. We establish that the presence of either D2L or D2S can support postsynaptic functions related to the control of motor activity in basal conditions. On the contrary, absence of D2S but not D2L prevents the inhibition of tyrosine hydroxylase phosphorylation and, thereby, of dopamine synthesis, supporting a major presynaptic role for D2S. Interestingly, boosting dopamine signaling in the striatum by acute cocaine administration reveals that absence of D2L, but not of D2S, strongly impairs the motor and cellular response to the drug, in a manner similar to the ablation of both isoforms. These results suggest that when the dopamine system is challenged, D2L signaling is required for the control of striatal circuits regulating motor activity. Thus, our findings show that D2L and D2S share similar functions in basal conditions but not in response to stimulation of the dopamine system.

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