scholarly journals Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval in rats

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Briac Halbout ◽  
Andrew T Marshall ◽  
Ali Azimi ◽  
Mimi Liljeholm ◽  
Stephen V Mahler ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Suppressive Effect ◽  
Maladaptive Behavior ◽  
Dopamine Neurons ◽  
Action Sequence ◽  
Reward Seeking ◽  
Fixed Action ◽  
Dopamine Circuits ◽  
Goal Directed Behavior

Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats’ mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.

scholarly journals Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval

2018 ◽  
Author(s):  
Briac Halbout ◽  
Andrew T. Marshall ◽  
Ali Azimi ◽  
Mimi Liljeholm ◽  
Stephen V. Mahler ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Suppressive Effect ◽  
Maladaptive Behavior ◽  
Dopamine Neurons ◽  
Action Sequence ◽  
Reward Seeking ◽  
Fixed Action ◽  
Dopamine Circuits ◽  
Goal Directed Behavior

AbstractEfficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.

scholarly journals Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

2022 ◽  
Author(s):  
Imre Kalló ◽  
Azar Omrani ◽  
Frank J. Meye ◽  
Han de Jong ◽  
Zsolt Liposits ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Medial Prefrontal Cortex ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Dopamine Neurons ◽  
Regulatory Processes ◽  
Ventral Tegmental ◽  
Shell Part

AbstractOrexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice

2020 ◽  
Vol 133 (2) ◽  
pp. 377-392
Author(s):  
Gaolin Qiu ◽  
Ying Wu ◽  
Zeyong Yang ◽  
Long Li ◽  
Xiaona Zhu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Medial Prefrontal Cortex ◽  
Repeated Measures ◽  
Intraperitoneal Injection ◽  
Dopamine Neurons ◽  
Patch Clamp Recording ◽  
Repeated Measures Anova ◽  
Ventral Tegmental

Background Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. Methods Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca2+ indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. Results Ca2+ signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, –0.745 [–1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, –0.498 [–0.664; –0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, –0.329 [–1.220; –0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). Conclusions Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action

2021 ◽  
Author(s):  
Laura L Grima ◽  
Marios C Panayi ◽  
Oliver Harmson ◽  
Emilie Syed ◽  
Sanjay G Manohar ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
D1 Receptors ◽  
Nucleus Accumbens Core ◽  
Action Sequence ◽  
Reward Seeking ◽  
Dopamine Transmission ◽  
Rapid Activation ◽  
Beneficial Outcome ◽  
Stimulation Of

While it is well established that dopamine transmission is integral in mediating the influence of reward expectations on reward-seeking actions, the precise causal role of dopamine transmission in moment-to-moment cue-driven behavioural control remains contentious. This is a particular issue in situations where it is necessary to refrain from responding to achieve a beneficial outcome. To examine this, we manipulated dopamine transmission pharmacologically as rats performed a Go/No-Go task that required them to either make or withhold action to gain either a small or large reward. Stimulation of D1Rs, both globally and locally in the nucleus accumbens core (NAcC) region consistently disrupted No-Go performance, potentiating inappropriate responses that clustered strongly just after cue presentation. D1R blockade did not, however, improve rats' ability to withhold responses, but instead primarily disrupted performance on Go trials. While global D1R blockade caused a general reduction of invigoration of reward seeking actions, intra-NAcC administration of the D1R antagonist by contrast increased the likelihood that Go trial performance was in an "unfocused" state. Such a state was characterised, both on and off drug, by a reduction in the precision and speed of responding even though the appropriate action sequence was often executed. These findings suggests that the balance of activity at NAcC D1Rs plays a key role in enabling the rapid activation of a focused, reward-seeking state to enable animals to efficiently and accurately achieve their goal.

scholarly journals The tubular striatum and nucleus accumbens distinctly represent reward-taking and seeking

2020 ◽  
Author(s):  
Katherine N. Wright ◽  
Daniel W Wesson
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Striatum ◽  
Neural Representation ◽  
Single Unit Activity ◽  
Self Administration ◽  
Reward Seeking ◽  
Motivated Behavior ◽  
Behavioral Paradigm ◽  
Motivated Behaviors ◽  
Goal Directed Behavior

The ventral striatum regulates motivated behaviors which are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. While background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and seeking.

scholarly journals Triadic model of the neurobiology of motivated behavior in adolescence

2005 ◽  
Vol 36 (3) ◽  
pp. 299-312 ◽  
Author(s):  
MONIQUE ERNST ◽  
DANIEL S. PINE ◽  
MICHAEL HARDIN
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Risk Taking ◽  
Novelty Seeking ◽  
Motivated Behavior ◽  
The Face ◽  
Goal Directed Behavior ◽  
Ventral Prefrontal Cortex ◽  
Triadic Model

Background. Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making.Method. We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed.Results. The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety.Conclusions. A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.

The galanin receptor-3 antagonist, SNAP 37889, inhibits cue-induced reinstatement of alcohol-seeking and increases c-Fos expression in the nucleus accumbens shell of alcohol-preferring rats

2018 ◽  
Vol 32 (8) ◽  
pp. 911-921 ◽  
Author(s):  
Kira-Elise Wilson ◽  
Sigrid Limburg ◽  
Melissa K Duggan ◽  
Adam J Lawther ◽  
Spencer J Williams ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Medial Prefrontal Cortex ◽  
Dopamine Neurons ◽  
Nucleus Accumbens Shell ◽  
Nucleus Accumbens Core ◽  
Fos Protein ◽  
Fos Expression ◽  
Dual Label ◽  
Alcohol Seeking

Introduction: This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats. Methods: Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.p.) or vehicle, before being tested for cue-induced reinstatement. Administration of SNAP 37889 reduced cue-induced reinstatement of ethanol-seeking behaviour. To examine the effect of SNAP 37889 and cue-induced reinstatement on neuronal activation, c-Fos expression was measured in subregions of the medial prefrontal cortex and nucleus accumbens. Results: SNAP 37889 administration increased c-Fos immunoreactivity in the nucleus accumbens shell, but was without effect in the nucleus accumbens core and the medial prefrontal cortex. Dual-label Fos/tyrosine hydroxylase immunohistochemistry was used to examine the effects of SNAP 37889 on dopamine neurons in the ventral tegmental area; however, no differences between SNAP 37889 and vehicle-treated rats were found. Conclusions: These data support previous findings of galanin-3 receptor involvement in cue-induced reinstatement of alcohol-seeking behaviour, and provide novel evidence that the ability of galanin-3 receptor antagonism to attenuate cue-induced reinstatement relates to activation of the nucleus accumbens shell.

scholarly journals Burst activation of dopamine neurons produces prolonged post-burst availability of actively released dopamine

2017 ◽  
Author(s):  
Sweyta Lohani ◽  
Adria K. Martig ◽  
Suzanne M. Underhill ◽  
Alicia DeFrancesco ◽  
Melanie J. Roberts ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Cognitive Functions ◽  
Dopamine Release ◽  
Dopamine Neurons ◽  
Dopamine Antagonists ◽  
Burst Stimulation ◽  
Multiple Timescales ◽  
Impulse Flow ◽  
Stimulation Of

SummaryBoth phasic and tonic modes of neurotransmission are implicated in critical functions assigned to dopamine. In learning, for example, sub-second phasic responses of ventral tegmental area (VTA) dopamine neurons to salient events serve as teaching signals, but learning is also interrupted by dopamine antagonists administered minutes after training. Our findings bridge the multiple timescales of dopamine neurotransmission by demonstrating that burst stimulation of VTA dopamine neurons produces a prolonged post-burst increase (> 20 min) of extracellular dopamine in nucleus accumbens and prefrontal cortex. This elevation is not due to spillover from the stimulation surge but depends on impulse flow-mediated dopamine release. We identified Rho-mediated internalization of dopamine transporter as a mechanism responsible for prolonged availability of actively released dopamine. These results demonstrate that phasic and tonic dopamine neurotransmission can be a continuum and may explain why both modes of signaling are critical for motivational and cognitive functions associated with dopamine.

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