scholarly journals A dynamic role for dopamine receptors in the control of mammalian spinal networks

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Simon A. Sharples ◽  
Nicole E. Burma ◽  
Joanna Borowska-Fielding ◽  
Charlie H. T. Kwok ◽  
Shane E. A. Eaton ◽  
...  
Keyword(s):  
Dopamine Receptors ◽  
Inhibitory Effect ◽  
Endogenous Dopamine ◽  
Co Activation ◽  
Dopaminergic Pathway ◽  
Network Output ◽  
Spinal Network ◽  
Specific Receptors ◽  
Differential Control ◽  
Parallel Activation

Abstract Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.

scholarly journals A dynamic role for dopamine receptors in the control of mammalian spinal networks

2019 ◽  
Author(s):  
Simon A. Sharples ◽  
Nicole E. Burma ◽  
Joanna Borowska-Fielding ◽  
Charlie H.T. Kwok ◽  
Shane E.A. Eaton ◽  
...  
Keyword(s):  
Neural Networks ◽  
Spinal Cord ◽  
Dopamine Receptors ◽  
Spontaneous Activity ◽  
Network Activity ◽  
Network State ◽  
Endogenous Dopamine ◽  
Network Output ◽  
Spinal Network

AbstractDopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors however; how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.Significance statementMonoaminergic neuromodulation of neural networks is dependent not only on target receptors but also on network state. We studied the concentration-dependent control of spinal networks of the neonatal mouse, in vitro, during a low excitability state characterized by spontaneous network activity. Spontaneous activity is an essential element for the development of networks. Under these conditions, we defined converging receptor and cellular mechanisms that contribute to the diverse, concentration-dependent control of spinal motor networks by dopamine, in vitro. These experiments advance understanding of how monoamines modulate neuronal networks under dynamically changing excitability conditions and provide evidence of dedicated D1 and D2 regulated network components in the spinal cord that are consistent with those reported in the striatum.

Aortic body chemoreceptor responses to dopamine, haloperidol, and pargyline

1982 ◽  
Vol 53 (3) ◽  
pp. 596-602 ◽  
Author(s):  
N. J. Smatresk ◽  
S. Lahiri
Keyword(s):  
Monoamine Oxidase ◽  
Partial Pressure ◽  
Dopamine Receptors ◽  
Inhibitory Effect ◽  
Dopamine Infusion ◽  
Arterial Partial Pressure ◽  
Endogenous Dopamine ◽  
Receptor Sites ◽  
Before And After ◽  
Responses To Dopamine

Aortic chemoreceptor activity, from single- or few-fiber afferent nerve preparations, was measured in response to dopamine and a dopaminergic blocker, haloperidol, in 18 anesthetized cats. In six of these cats the effect of dopamine was assessed before and after inhibiting monoamine oxidase (MAO) by pargyline. Intravenous dopamine infusion (713;14 microgram X kg-1 X min-1) had a generally inhibitory effect on aortic chemoreceptor activity, but the magnitude of this effect varied with arterial partial pressure of O2 (Pao2) levels. The inhibitory effect of dopamine increased as Pao2 levels fell, and at severely hypoxic Pao2 levels (below 30 Torr) exogenous dopamine had no significant effect. The inhibitory effect of dopamine also increased during hyperoxic hypercapnia. Blockade of dopamine receptors in the aortic body by haloperidol-stimulated chemoreceptor activity significantly during hypoxia, suggesting an O2-dependent release of dopamine from the aortic body as Pao2 falls. Inhibition of MAO by pargyline had no significant effect on the control rate of activity at any level of Pao2 but augmented the inhibitory effect of exogenously administered dopamine. These data indicate that MAO is not significantly involved in the degradation of endogenous dopamine at the aortic receptor sites, but may participate in the degradation of exogenous dopamine.

scholarly journals Endogenous Dopamine Suppresses Initiation of Swimming in Prefeeding Zebrafish Larvae

2008 ◽  
Vol 100 (3) ◽  
pp. 1635-1648 ◽  
Author(s):  
Vatsala Thirumalai ◽  
Hollis T. Cline
Keyword(s):  
D2 Receptor ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Resting Membrane Potential ◽  
Downstream Target ◽  
Zebrafish Larvae ◽  
Endogenous Dopamine ◽  
Dopamine Reuptake ◽  
Episode Frequency ◽  
The Brain

Dopamine is a key neuromodulator of locomotory circuits, yet the role that dopamine plays during development of these circuits is less well understood. Here, we describe a suppressive effect of dopamine on swim circuits in larval zebrafish. Zebrafish larvae exhibit marked changes in swimming behavior between 3 days postfertilization (dpf) and 5dpf. We found that swim episodes were fewer and of longer durations at 3 than at 5dpf. At 3dpf, application of dopamine as well as bupropion, a dopamine reuptake blocker, abolished spontaneous fictive swim episodes. Blocking D2 receptors increased frequency of occurrence of episodes and activation of adenylyl cyclase, a downstream target inhibited by D2-receptor signaling, blocked the inhibitory effect of dopamine. Dopamine had no effect on motor neuron firing properties, input impedance, resting membrane potential, or the amplitude of spike afterhyperpolarization. Application of dopamine either to the isolated spinal cord or locally within the cord does not decrease episode frequency, whereas dopamine application to the brain silences episodes, suggesting a supraspinal locus of dopaminergic action. Treating larvae with 10 μM MPTP reduced catecholaminergic innervation in the brain and increased episode frequency. These data indicate that dopamine inhibits the initiation of fictive swimming episodes at 3dpf. We found that at 5dpf, exogenously applied dopamine inhibits swim episodes, yet the dopamine reuptake blocker or the D2-receptor antagonist have no effect on episode frequency. These results led us to propose that endogenous dopamine release transiently suppresses swim circuits in developing zebrafish.

Fusing languages in the bilingual cognitive architecture

2016 ◽  
Vol 19 (5) ◽  
pp. 879-880 ◽  
Author(s):  
SUSAN C. BOBB ◽  
NORIKO HOSHINO
Keyword(s):  
Brain Plasticity ◽  
Selection Process ◽  
Cognitive Architecture ◽  
Code Switching ◽  
Cognitive System ◽  
Co Activation ◽  
Perceived Difficulty ◽  
Key Factor ◽  
Bilingual Speaker ◽  
Parallel Activation

Research on bilingualism has documented profound brain plasticity by which the bilingual experience reconfigures the cognitive system. These effects include temporary as well as more enduring ones, and parallel activation of a bilingual's two languages may well be a key factor at the root of these observed changes. Recent recommendations (Green, 2011) have emphasized that research on code-switching in particular could provide a fruitful avenue for investigating the nature of how a bilingual speaker selects words and ultimately produces an utterance. Findings to date illustrate that if anything, the reach of co-activation is more extensive than previously thought, extending to the phonology and syntax of languages. While the degree of permeability may compound the perceived difficulty of the selection process, it is also a testament to the documented mental agility of bilinguals.

scholarly journals Time-dependence of biological activity induced by covalent insulin-receptor complexes in rat adipocytes

1985 ◽  
Vol 232 (1) ◽  
pp. 49-53 ◽  
Author(s):  
A Schüttler ◽  
C Diaconescu ◽  
D J Saunders ◽  
D Brandenburg
Keyword(s):  
Insulin Receptor ◽  
Inhibitory Effect ◽  
Receptor Complex ◽  
Half Time ◽  
Simple Method ◽  
Receptor Complexes ◽  
Maximal Stimulation ◽  
Monocomponent Insulin ◽  
Specific Receptors ◽  
Stimulation Of

Lipogenesis in isolated adipocyte preparations is stimulated when photosensitive insulin derivatives are attached covalently to specific receptors. This response was compared quantitatively with that to reversibly associated insulin, and it was shown that both covalent and reversible insulin-receptor complexes behave very similarly. The extent of stimulation of lipogenesis was studied as a function of time. Cells were incubated in buffer for various times before addition to vials containing 0 (basal) or 10 ng of monocomponent insulin/ml (maximal) and [U-3H]glucose. After 60 min, the toluene-soluble [3H]lipids were measured. The maximal stimulation induced by reversibly bound insulin was virtually constant over a period of 4 h. In contrast, adipocytes to which N alpha B2-(2-nitro-4-azidophenylacetyl)-des-PheB1-insulin had been covalently attached at the start of the experiment showed a loss of stimulation with time when incubated at 37 degrees C. This loss was decreased in the presence of lysosomotropic agents such as chloroquine at concentrations (approx. 200 microM) that had very little or no effect on the basal and maximal lipogenesis rates. A simple method was used to transform the measured rate of loss of stimulation into a rate of loss of effective units. A half-time of 80 min was calculated for the effective covalent insulin-receptor units in adipocytes at 37 degrees C at pH 7.4. This is very close to values reported by others for the internalization of covalent complexes in these cells, suggesting that this may be the causative event for the deactivation of the insulin-receptor unit. The inhibitory effect of chloroquine on the deactivation may indicate that the insulin-receptor complex can function even after internalization.

scholarly journals Activation of the dopaminergic pathway from VTA to the medial olfactory tubercle generates odor-preference and reward

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zhijian Zhang ◽  
Qing Liu ◽  
Pengjie Wen ◽  
Jiaozhen Zhang ◽  
Xiaoping Rao ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Receptors ◽  
Neural Circuit ◽  
Life Experiences ◽  
Olfactory Tubercle ◽  
Odor Preference ◽  
Dopaminergic Pathway ◽  
Different Types ◽  
Pharmacological Blockade ◽  
Odor Preferences

Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.

scholarly journals Amphetamine Promotes Cortical Up State in Part Via Dopamine Receptors

2021 ◽  
Vol 12 ◽  
Author(s):  
Guofang Shen ◽  
Wei-Xing Shi
Keyword(s):  
General Anesthesia ◽  
Dopamine Receptors ◽  
Cortical Neurons ◽  
Slow Wave Sleep ◽  
Field Potential ◽  
Promoting Effect ◽  
Hyperactivity Disorder ◽  
Co Activation ◽  
Potential Recording ◽  
The Difference

Cortical neurons oscillate between Up and Down states during slow wave sleep and general anesthesia. Recent studies show that Up/Down oscillations also occur during quiet wakefulness. Arousal eliminates Down states and transforms Up/Down oscillations to a persistent Up state. Further evidence suggests that Up/Down oscillations are crucial to memory consolidation, whereas their transition to a persistent Up state is essential for arousal and attention. We have shown that D-amphetamine promotes cortical Up state, and the effect depends on activation of central α1A adrenergic receptors. Here, we report that dopamine also plays a role in D-amphetamine’s effect. Thus, using local-field-potential recording in the prefrontal cortex in chloral hydrate-anesthetized rats, we showed that the Up-state promoting effect of D-amphetamine was attenuated by antagonists at either D1 or D2-like dopamine receptors. The effect was also partially mimicked by co-activation of D1 and D2-like receptors. These results are consistent with the fact that D-amphetamine increases the release of both norepinephrine and dopamine. They are also in agreement with studies showing that dopamine promotes wakefulness and mediates D-amphetamine-induced emergence from general anesthesia. The effect of D-amphetamine was not mimicked, however, by activation of either D1 or D2-like receptors alone, indicating an interdependence between D1 and D2-like receptors. The dopamine/norepinephrine precursor L-DOPA also failed to promote the Up state. While more studies are needed to understand the difference between L-DOPA and D-amphetamine, our finding may provide an explanation for why L-DOPA lacks significant psychostimulant properties and is ineffective in treating attention-deficit/hyperactivity disorder.

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