Prefrontal cortical and nucleus accumbens contributions to discriminative conditioned suppression of reward-seeking

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.

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Activation of Prefrontal Cortical Parvalbumin Interneurons Facilitates Extinction of Reward-Seeking Behavior

Journal of Neuroscience ◽

10.1523/jneurosci.0235-13.2014 ◽

2014 ◽

Vol 34 (10) ◽

pp. 3699-3705 ◽

Cited By ~ 53

Author(s):

D. R. Sparta ◽

N. Hovelso ◽

A. O. Mason ◽

P. A. Kantak ◽

R. L. Ung ◽

...

Keyword(s):

Prefrontal Cortical ◽

Reward Seeking ◽

Parvalbumin Interneurons ◽

Seeking Behavior

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Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

10.1101/520817 ◽

2019 ◽

Cited By ~ 3

Author(s):

Anne L. Collins ◽

Tara J. Aitken ◽

I-Wen Huang ◽

Christine Shieh ◽

Venuz Y. Greenfield ◽

...

Keyword(s):

Nucleus Accumbens ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Female Rats ◽

Nucleus Accumbens Core ◽

Cholinergic Interneurons ◽

Reward Seeking ◽

Motivated Behavior ◽

Male And Female Rats ◽

Seeking Behavior

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.

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

10.1101/2021.06.15.448563 ◽

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.

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

Journal of Neurophysiology ◽

10.1152/jn.00495.2020 ◽

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.

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