scholarly journals Glucose-sensing in AgRP neurons integrates homeostatic energy state with dopamine signalling in the striatum.

2021 ◽  
Author(s):  
Alex Reichenbach ◽  
Rachel Clarke ◽  
Romana Stark ◽  
Sarah H Lockie ◽  
Mathieu Mequinion ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Energy State ◽  
Dorsal Striatum ◽  
Glucose Sensing ◽  
Low Energy ◽  
Metabolic Enzyme ◽  
Acid Oxidation ◽  
Operant Responding ◽  
Electrophysiological Studies

Hunger increases the motivation of an organism to seek out and consume highly palatable energy dense foods by acting on the midbrain dopaminergic system. Here, we identify a novel molecular mechanism through which hunger-sensing AgRP neurons detect low energy availability and modulate dopamine release to increase motivation for food reward. We tested the hypothesis that carnitine acetyltransferase (Crat), a metabolic enzyme regulating glucose and fatty acid oxidation, in AgRP neurons is necessary to sense low energy states and regulate motivation for food rewards by modulating accumbal or striatal dopamine release. In support of this, electrophysiological studies show that AgRP neurons require Crat for appropriate glucose-sensing. Intact glucose-sensing in AgRP neurons controls post-ingestive dopamine accumulation in the dorsal striatum. Fibre photometry experiments, using the dopamine sensor GRABDA, revealed that impaired glucose-sensing, in mice lacking Crat in AgRP neurons, reduces dopamine release in the nucleus accumbens to palatable food consumption and during operant responding, particularly in the fasted state. Finally, the reduced dopamine release in the nucleus accumbens of mice lacking Crat in AgRP neurons affects sucrose preference and motivated operant responding for sucrose rewards. Notably, these effects are potentiated in the hungry state and therefore highlight that glucose-sensing by Crat in AgRP neurons is required for the appropriate integration and transmission of homeostatic hunger-sensing to dopamine signalling in the striatum. These studies offer a novel molecular target to control the overconsumption of palatable foods in a population of hunger-sensing AgRP neurons.

scholarly journals Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Alex Reichenbach ◽  
Rachel E Clarke ◽  
Romana Stark ◽  
Sarah H Lockie ◽  
Mathieu Mequinion ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Ex Vivo ◽  
Temporal Integration ◽  
Dorsal Striatum ◽  
Glucose Sensing ◽  
Palatable Food ◽  
Operant Responding ◽  
Metabolic Sensing ◽  
Homeostatic State

Agouti-related peptide (AgRP) neurons increase motivation for food, however whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase (Crat) in mice. We hypothesized that metabolic sensing in AgRP neurons is required to increase motivation for food reward by modulating accumbal or striatal dopamine release. Studies confirmed that Crat deletion in AgRP neurons (KO) impaired ex vivo glucose-sensing, as well as in vivo responses to peripheral glucose injection or repeated palatable food presentation and consumption. Impaired metabolic-sensing in AgPP neurons reduced acute dopamine release (seconds) to palatable food consumption and during operant responding, as assessed by GRAB-DA photometry in the nucleus accumbens, but not the dorsal striatum. Impaired metabolic-sensing in AgRP neurons suppressed radiolabelled 18F-fDOPA accumulation after ~30 minutes in the dorsal striatum but not the nucleus accumbens. Impaired metabolic sensing in AgRP neurons suppressed motivated operant responding for sucrose rewards during fasting. Thus, metabolic-sensing in AgRP neurons is required for the appropriate temporal integration and transmission of homeostatic hunger-sensing to dopamine signalling in the striatum.

scholarly journals Differences in Nicotine Encoding Dopamine Release between the Striatum and Shell Portion of the Nucleus Accumbens

2018 ◽  
Vol 28 (3) ◽  
pp. 248-261 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Bon-Jour Lin ◽  
Tsung-Hsun Hsieh ◽  
Tung-Tai Kuo ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
High Frequency ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Frequency Stimulation ◽  
Da Release

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

scholarly journals Age-dependent effects of protein restriction on dopamine release

2020 ◽  
Vol 46 (2) ◽  
pp. 394-403
Author(s):  
Fabien Naneix ◽  
Kate Z. Peters ◽  
Andrew M. J. Young ◽  
James E. McCutcheon
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Physiological State ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Protein Restriction ◽  
Fast Scan Cyclic Voltammetry ◽  
Health And Development ◽  
Late Maturation ◽  
The Impact

AbstractDespite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1–20 Hz). By contrast, protein restriction during adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction at adulthood has no impact on dopamine release but the same diet during adolescence induced a frequency-dependent increase in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

scholarly journals Kinetic features of the dopamine release and uptake in the dorsal and ventral striatum of rats

2020 ◽  
Vol 19 (4) ◽  
pp. 47-54
Author(s):  
Valery N. Mukhin ◽  
Ivan R. Borovets ◽  
Vadim V. Sizov ◽  
Konstantin I. Pavlov ◽  
Victor M. Klimenko
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Principal Component ◽  
Dopamine Uptake ◽  
Rat Striatum ◽  
The Core ◽  
Kinetics Of

Kinetics of the evoked dopamine release and subsequent uptake in the parts of the rat striatum has not been studied sufficiently. The aim of this study is to fill this gap and to investigate kinetics of dopamine release and uptake in vivo so that comparison can be made between the dorsal and the parts of the ventral striatum and with taking into account the overlapping electrochemical factors during the subsequent analysis of voltammetry recordings. Materials and methods. The evoked wave of dopamine release and uptake in the dorsal striatum, core, and shell of the nucleus accumbens in the different groups of rats was recorded by the fast-scan cyclic voltammetry. Voltammetry recordings were subjected to principal component analysis and only the components associated with dopamine were taken for further analysis. The values of the parameters of the curves of dopamine release and uptake were defined. Then factor and variance analyses of the parameters were carried out. Results. Factor analysis showed that the set of parameters of the dopamine wave can be reduced to the 4 factors that are comparable with the variables of the known from the literature mathematical model that describes the dopamine wave based on the MichaelisMenten equation. Two of the factors and the corresponding parameters of the dopamine curve differ within the dorsal and ventral striatum. Factor 1 is associated with the parameters HL, T80_20, T20_0, slope_T20T0, which are significantly larger in the core of the nucleus accumbens. Factor 3 is associated with the parameters T50_2, AUC, FWHH, T100_80 which are significantly less in the dorsal striatum. Conclusions. The parameters of the curve of dopamine release and uptake are determined by 4 factors. Among the dopamine curve parameters, the best measures of the factors are T50_1, DAC, T100_80 и T20_0. The kinetics of stimulated dopamine release and uptake varies within the dorsal and ventral striatum. The final phase of dopamine uptake is slowed in the core of the nucleus accumbens in comparison to the shell, and the dorsal striatum. The slope of initial phase of dopamine uptake in the dorsal striatum is steeper.

scholarly journals Age dependent effects of protein restriction on dopamine release

2020 ◽  
Author(s):  
Fabien Naneix ◽  
Kate Z. Peters ◽  
Andrew M. J. Young ◽  
James E. McCutcheon
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Physiological State ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Protein Restriction ◽  
Fast Scan Cyclic Voltammetry ◽  
Health And Development ◽  
Late Maturation ◽  
The Impact

ABSTRACTDespite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1-20 Hz). By contrast, protein restriction performed at adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction has no impact on dopamine release when performed at adulthood but in adolescent rats we observed frequency-dependent increases in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

Modulation of Somatodendritic Dopamine Release by Endogenous H2O2: Susceptibility in Substantia Nigra But Resistance in VTA

2002 ◽  
Vol 87 (2) ◽  
pp. 1155-1158 ◽  
Author(s):  
Billy T. Chen ◽  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Substantia Nigra Pars Compacta ◽  
Fast Scan Cyclic Voltammetry ◽  
Carbon Fiber Microelectrodes ◽  
Da Release ◽  
Striking Contrast

We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H2O2). Here, we examined whether endogenous H2O2 can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenous H2O2decreased DA release by 50–60% in SNc and VTA but only by 35% in nucleus accumbens. Whether endogenous H2O2 also modulated somatodendritic release was examined using the glutathione peroxidase inhibitor, mercaptosuccinate (MCS), which should increase stimulation-evoked H2O2levels. In the presence of MCS, DA release was suppressed by 30–40% in SNc as well as in dorsal striatum and nucleus accumbens. In striking contrast, DA release in the VTA was unaffected by MCS. These data are consistent with stronger H2O2 regulation or lower H2O2 generation in VTA than in the other regions. Importantly, oxidative stress has been linked causally to Parkinson's disease, in which DA cells in SNc degenerate, but VTA cells are spared. The present data suggest that differences in oxidant regulation or generation between SNc and VTA could contribute to this.

scholarly journals A pain-induced tonic hypodopaminergic state augments phasic dopamine release in the nucleus accumbens

Pain ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Taylor A. Gee ◽  
Nathan C. Weintraub ◽  
Dong Lu ◽  
Caroline E. Phelps ◽  
Edita Navratilova ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

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