scholarly journals Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

2015 ◽  
Vol 112 (30) ◽  
pp. 9472-9477 ◽  
Author(s):  
David E. Moorman ◽  
Gary Aston-Jones
Keyword(s):  
Single Neuron ◽  
Lever Press ◽  
Contextual Information ◽  
Behavioral Responses ◽  
Conservation Of Energy ◽  
Reward Seeking ◽  
Cocaine Seeking ◽  
Medial Pfc ◽  
Evoked Activity ◽  
Goal Directed Behavior

The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not.

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 Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

2019 ◽  
Author(s):  
Koral Goltseker ◽  
Hen Handrus ◽  
Segev Barak
Keyword(s):  
Memory Retrieval ◽  
Lever Press ◽  
Water Flooding ◽  
Memory Reconsolidation ◽  
Place Conditioning ◽  
Self Administration ◽  
Conditioning Paradigm ◽  
Cocaine Seeking ◽  
Lever Pressing ◽  
Alcohol Seeking

AbstractRelapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a “reconsolidation” process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addiction-related behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol-memory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after alcohol-memory retrieval. Furthermore, rats trained to lever-press for alcohol showed decreased context-induced renewal of alcohol-seeking responding when the lever-pressing was counterconditioned with foot-shocks, shortly, but not 6 h, after memory retrieval. These results 0suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol-memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Also, we found that aversive counterconditioning preceded by alcohol-memory retrieval was characterized by upregulation of brain-derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that Bdnf plays a role in the memory updating process.

scholarly journals Context-dependent decision making in a premotor circuit

2019 ◽  
Author(s):  
Zheng Wu ◽  
Ashok Litwin-Kumar ◽  
Philip Shamash ◽  
Alexei Taylor ◽  
Richard Axel ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Contextual Information ◽  
Sensory Information ◽  
Behavioral Responses ◽  
Association Cortex ◽  
Match To Sample ◽  
Subsequent Test ◽  
Layer 2 ◽  
Test Odor ◽  
Context Dependent

SummaryCognitive capacities afford contingent associations between sensory information and behavioral responses. We studied this problem using an olfactory delayed match to sample task whereby a sample odor specifies the association between a subsequent test odor and rewarding action. Multi-neuron recordings revealed representations of the sample and test odors in olfactory sensory and association cortex, which were sufficient to identify the test odor as match/non-match. Yet, inactivation of a downstream premotor area (ALM), but not orbitofrontal cortex, confined to the epoch preceding the test odor, led to gross impairment. Olfactory decisions that were not context dependent were unimpaired. Therefore, ALM may not receive the outcome of a match/non-match decision from upstream areas but contextual information—the identity of the sample—to establish the mapping between test odor and action. A novel population of pyramidal neurons in ALM layer 2 may mediate this process.

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.

Reward-related processing in the human brain: Developmental considerations

2008 ◽  
Vol 20 (4) ◽  
pp. 1191-1211 ◽  
Author(s):  
Dominic S. Fareri ◽  
Laura N. Martin ◽  
Mauricio R. Delgado
Keyword(s):  
Unprotected Sex ◽  
Maladaptive Behaviors ◽  
Risky Decision ◽  
Reward Circuitry ◽  
Hyperactivity Disorder ◽  
Reward Seeking ◽  
Atypical Development ◽  
Developmental Conditions ◽  
Goal Directed Behavior

AbstractThe pursuit of rewarding experiences motivates everyday human behavior, and can prove beneficial when pleasurable, positive consequences result (e.g., satisfying hunger, earning a paycheck). However, reward seeking may also be maladaptive and lead to risky decisions with potentially negative long-term consequences (e.g., unprotected sex, drug use). Such risky decision making is often observed during adolescence, a time in which important structural and functional refinements occur in the brain's reward circuitry. Although much of the brain develops before adolescence, critical centers for goal-directed behavior, such as frontal corticobasal ganglia networks, continue to mature. These ongoing changes may underlie the increases in risk-taking behavior often observed during adolescence. Further, typical development of these circuits is vital to our ability to make well-informed decisions; atypical development of the human reward circuitry can have severe implications, as is the case in certain clinical and developmental conditions (e.g., attention-deficit/hyperactivity disorder). This review focuses on current research probing the neural correlates of reward-related processing across human development supporting the current research hypothesis that immature or atypical corticostriatal circuitry may underlie maladaptive behaviors observed in adolescence.

scholarly journals Dynamic CRMP2 regulation of CaV2.2 in the prefrontal cortex contributes to the reinstatement of cocaine seeking

2019 ◽  
Author(s):  
William C. Buchta ◽  
Aubin Moutal ◽  
Bethany Hines ◽  
Constanza Garcia-Keller ◽  
Alexander C.W. Smith ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Treatment Options ◽  
Health Concern ◽  
Self Administration ◽  
Drug Seeking ◽  
Binding Partner ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Medial Pfc

AbstractCocaine addiction is a major health concern with limited effective treatment options. A better understanding of mechanisms underlying relapse may help inform the development of new pharmacotherapies. Emerging evidence suggests that collapsin response mediator protein 2 (CRMP2) regulates presynaptic excitatory neurotransmission and contributes to pathological changes during diseases, such as neuropathic pain and substance use disorders. We examined the role of CRMP2 and its interactions with a known binding partner, CaV2.2, in cocaine-seeking behavior. We employed the rodent self-administration model of relapse to drug-seeking and focused on the prefrontal cortex (PFC) for its well-established role in reinstatement behaviors. Our results indicated that repeated cocaine self-administration resulted in a dynamic and persistent alteration in the PFC expression of CRMP2 and its binding partner, the CaV2.2 (N-type) voltage-gated calcium channel. Following cocaine self-administration and extinction training, the expression of both CRMP2 and CaV2.2 was reduced relative to Yoked saline controls. By contrast, cued-reinstatement potentiated CRMP2 expression and increased CaV2.2 expression above extinction levels. Lastly, we utilized the recently developed peptide myr-TAT-CBD3 to disrupt the interaction between CRMP2 and CaV2.2 in vivo. We assessed the reinstatement behavior after infusing this peptide directly into the medial PFC and found that it decreased cue-induced reinstatement of cocaine seeking. Taken together, these data suggest that neuroadaptations in the CRMP2/CaV2.2 signaling cascade in the PFC can facilitate drug seeking behavior. Targeting such interactions has implications for the treatment of cocaine relapse behavior.

scholarly journals Monosynaptic Retrograde Tracing From Prelimbic Neuron Subpopulations Projecting to Either Nucleus Accumbens Core or Rostromedial Tegmental Nucleus

2021 ◽  
Vol 15 ◽  
Author(s):  
Adelis M. Cruz ◽  
Tabitha H. Kim ◽  
Rachel J. Smith
Keyword(s):  
Nucleus Accumbens ◽  
Primary Source ◽  
Nucleus Accumbens Core ◽  
Cortical Input ◽  
Reward Seeking ◽  
Tegmental Nucleus ◽  
Rostromedial Tegmental Nucleus ◽  
Cocaine Seeking ◽  
Mediodorsal Thalamic Nucleus ◽  
Motivated Behaviors

The prelimbic (PL) region of the medial prefrontal cortex (mPFC) has been implicated in both driving and suppressing motivated behaviors, including cocaine-seeking in rats. These seemingly opposing functions may be mediated by different efferent targets of PL projections, such as the nucleus accumbens (NAc) core and rostromedial tegmental nucleus (RMTg), which have contrasting roles in reward-seeking behaviors. We sought to characterize the anatomical connectivity differences between PL neurons projecting to NAc core and RMTg. We used conventional retrograde tracers to reveal distinct subpopulations of PL neurons projecting to NAc core vs. RMTg in rats, with very little overlap. To examine potential differences in input specificity for these two PL subpopulations, we then used Cre-dependent rabies virus (EnvA-RV-EGFP) as a monosynaptic retrograde tracer and targeted specific PL neurons via injections of retrograde CAV2-Cre in either NAc core or RMTg. We observed a similar catalog of cortical, thalamic, and limbic afferents for both NAc- and RMTg-projecting populations, with the primary source of afferent information arising from neighboring prefrontal neurons in ipsilateral PL and infralimbic cortex (IL). However, when the two subpopulations were directly compared, we found that RMTg-projecting PL neurons received a greater proportion of input from ipsilateral PL and IL, whereas NAc-projecting PL neurons received a greater proportion of input from most other cortical areas, mediodorsal thalamic nucleus, and several other subcortical areas. NAc-projecting PL neurons also received a greater proportion of contralateral cortical input. Our findings reveal that PL subpopulations differ not only in their efferent target but also in the input specificity from afferent structures. These differences in connectivity are likely to be critical to functional differences of PL subpopulations.

scholarly journals Conditioned Aversion for a Cocaine-Predictive Cue is Associated withCocaine Seeking and Taking in Rats

2014 ◽  
Vol 27 (3) ◽  
Author(s):  
Elizabeth M. Colechio ◽  
Patricia S. Grigson
Keyword(s):  
Individual Differences ◽  
Cue Reactivity ◽  
Conditioned Aversion ◽  
Self Administration ◽  
Taste Reactivity ◽  
Aversive Taste ◽  
Cocaine Seeking ◽  
Trial Basis ◽  
Goal Directed Behavior

Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue, and greater conditioned aversive TR in well-trained rats predicts greater drug-taking. Here, we used a between-groups design and tracked the development of this conditioned aversive TR behavior on a trial by trial basis in an effort to determine when the change in behavior occurs and at what point individual differences in cue reactivity become predictive of cocaine-seeking and cocaine-taking. The results demonstrate that conditioned aversive TR to a cocaine-predictive flavor cue appears very early in training (i.e., following as few as 1 – 2 taste-drug pairings), stabilizes quickly, and becomes predictive of “terminal” self-administration within 3 – 4 trials. Indeed, rats exhibiting high conditioned aversive TR to the cocaine-paired cue also exhibited greater goal-directed behavior, were faster to take drug, self-administered more cocaine, and exhibited greater seeking during periods of drug non-availability. High conditioned aversive TR, then, develops quickly and is indicative of a greater motivation for drug.

scholarly journals Reading Emotions, Reading People: Emotion Perception and Inferences Drawn from Perceived Emotions

2021 ◽  
Author(s):  
Jens Lange ◽  
Marc Heerdink ◽  
Gerben van Kleef
Keyword(s):  
Social Interaction ◽  
Contextual Information ◽  
Behavioral Responses ◽  
Emotion Perception ◽  
The Self ◽  
Future Research ◽  
Emotional Expressions ◽  
Coordinated Action

Emotional expressions play an important role in coordinating social interaction. We review research on two critical processes that underlie such coordination: (1) perceiving emotions from emotion expressions and (2) drawing inferences from perceived emotions. Broad evidence indicates that (a) observers can accurately perceive emotions from a person’s facial, bodily, vocal, verbal, and symbolic expressions, and that such emotion perception is further informed by contextual information. Moreover, (b) observers draw consequential and contextualized inferences from these perceived emotions about the expresser, the situation, and the self. Thus, emotion expressions enable coordinated action by providing information that facilitates adaptive behavioral responses. We recommend that future research investigate how people integrate information from different expressive modalities and how this affects consequential inferences.

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.

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