<i>Dopamine Signaling in the Dorsal Striatum Is Essential for Motivated Behaviors</i>

Palmiter, Richard D.

doi:10.1196/annals.1417.003

Cited by 335 publications

(333 citation statements)

References 71 publications

(215 reference statements)

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“…However, motivation to engage in the tasks is significantly altered in these mice, suggesting that DA mediates ''wanting'' rewards, rather than learning (17). For example, DA-deficient mice appear to be unmotivated and will not engage in most tasks (49), whereas hyperdopaminergic mice perform some tasks more rapidly with less meandering, suggesting enhanced motivation (13). We observed longer latencies by the KO mice to make choices and engage in goal-directed behavior in many learning paradigms, suggesting that they may be less motivated in the absence of burst firing.…”

Section: Discussionmentioning

confidence: 99%

Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior

Zweifel

Parker

Lobb

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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383

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Midbrain dopamine (DA) neurons fire in 2 characteristic modes, tonic and phasic, which are thought to modulate distinct aspects of behavior. However, the inability to selectively disrupt these patterns of activity has hampered the precise definition of the function of these modes of signaling. Here, we addressed the role of phasic DA in learning and other DA-dependent behaviors by attenuating DA neuron burst firing and subsequent DA release, without altering tonic neural activity. Disruption of phasic DA was achieved by selective genetic inactivation of NMDA-type, ionotropic glutamate receptors in DA neurons. Disruption of phasic DA neuron activity impaired the acquisition of numerous conditioned behavioral responses, and dramatically attenuated learning about cues that predicted rewarding and aversive events while leaving many other DA-dependent behaviors unaffected.cue-dependent learning ͉ mouse behavior ͉ electrophysiology ͉ cyclic voltammetry D opamine (DA) neurons of the ventral midbrain project to the dorsal and ventral striatum, as well as to other corticolimbic structures such as the hippocampus, amygdala, and prefrontal cortex. Differential DA release (tonic or phasic) is thought to activate distinct signal transduction cascades through the activation of postsynaptic inhibitory and excitatory G protein coupled receptors. Phasic DA is proposed to activate excitatory, low-affinity DA D1-like receptors (Rs) (1, 2) to facilitate long-term potentiation of excitatory synaptic transmission and enhance activity of the basal ganglia direct pathway facilitating appropriate action selection during goal-directed behavior. Conversely, tonic DA release is proposed to act on inhibitory, high-affinity DA D2Rs to facilitate long-term depression of cortico-striatal synapses and suppress activity of medium spiny neurons (MSNs) of the basal ganglia indirect pathway (1, 3-5). Thus, coordinate D1R and D2R activation modulates motor and cognitive function, and facilitates behavioral flexibility by a dichotomous control of striatal plasticity (5).During reinforcement learning shifts in phasic DA neuron responses from primary rewards, to reward predicting, stimuli are thought to reflect the acquisition of incentive salience for the predictive conditioned stimuli (6-10). Coincident DA and glutamate release onto MSNs during conditioned-stimulus response learning facilitates long-term potentiation of excitatory synapses that is thought to underlie reinforcement learning (1, 2, 11). Pharmacological or genetic disruption of D1R signaling impairs learning in numerous behavioral paradigms (2, 11); thus, phasic DA acting through D1R is thought to facilitate memory acquisition by ''stamping-in'' stimulus-response associations.Although considerable correlative electrophysiological evidence, as well as pharmacological and genetic evidence, supports an important role of phasic DA in stamping-in cue-reward associations, other evidence suggests that DA is not necessary for learning conditioned-stimulus responses. Mice genetically modified to...

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Section: Discussionmentioning

confidence: 99%

Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior

Zweifel

Parker

Lobb

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

383

425

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“…DA is also involved with the motivation to perform behaviours necessary to procure and consume the food. In fact, DA-deficient mice are hypophagic, fail to engage in goaldirected feeding behaviours, and will die of starvation (Palmiter, 2008;Szczypka et al, 1999). Moreover, it was found that chemical lesions of the DA system (pharmacological antagonists of DA receptor), sufficient to inhibit food-seeking behaviour, did not affect the pleasure reactions to sucrose placed in the mouth (Berridge and Robinson, 1998;Tyrka et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Mesolimbic lipid sensing and the regulation of feeding behaviour

Cansell

Luquet²

2015

OCL

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-In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Despite genetic predisposition, obesity often involves a behavioral component in which, similar to drugs of abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. Food intake is modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a main actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the mesolimbic pathway.Keywords: Obesity / tryglicerides / feeding behavior / reward / lipoprotein lipase Résumé -La détection des lipides par le système mésolimbique et la régulation des comportements alimentaires. Dans les pays développés et en voie de développement la sédentarisation des populations et la surexposition aux nourritures riche en énergie conduisent à la mise en place d'un déséquilibre énergétique et à l'obésité. Bien qu'il existe des prédispositions génétiques, l'obésité implique souvent des comportements compulsifs face à la nourriture, similaires aux drogues d'abus, qui entraînent une consommation de nourriture supérieure aux besoins éner-gétiques de l'organisme. L'hypothalamus est le premier site d'intégration des facteurs circulants qui reflètent le statut énergétique de l'organisme, il est donc considéré comme un des acteurs principaux dans la régulation centrale de la balance énergétique. Cependant, la prise alimentaire est également régulée par des facteurs sensoriels ou affectifs et le système mesolimbique est reconnu pour être un des systèmes majeurs dans la régulation de récompense associée à la prise alimentaire. Plus spécifiquement, les aspects motivationnels et hédoniques de la prise alimentaire sont étroitement liés à la libération de dopamine (DA) notamment dans le noyau accumbens. Plusieurs études montrent qu'à la fois chez l'...

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“…DA is also involved with the motivation to perform the behaviors necessary to procure and consume the food. In fact, Dopamine-deficient mice are hypophagic, fail to engage in goaldirected feeding behaviors, and will die of starvation (Szczypka et al, 1999;Palmiter, 2008). If DA signaling is restored only to the Cpu, mice will eat sufficiently for survival, whereas restoration of DA in the Nacc is not sufficient to sustain long-term feeding (Szczypka et al, 2001;Palmiter, 2008).…”

Section: Hypothalamic Sensing Of Lcfas and Metabolic Syndromementioning

confidence: 99%