scholarly journals Functional independence of endogenous µ- and δ-opioid receptors co-expressed in cholinergic interneurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Seksiri Arttamangkul ◽  
Emily J Platt ◽  
James Carroll ◽  
David Farrens
Keyword(s):  
Nucleus Accumbens ◽  
Prediction Error ◽  
Computational Modelling ◽  
Functional Independence ◽  
Adaptive Behaviour ◽  
Extinction Learning ◽  
Behavioural Treatment ◽  
Cholinergic Interneurons ◽  
Related Pathway ◽  
Time Point

Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.

scholarly journals L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Roland Esser ◽  
Christoph W Korn ◽  
Florian Ganzer ◽  
Jan Haaker
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Prediction Error ◽  
Computational Modelling ◽  
Ventromedial Prefrontal Cortex ◽  
Adaptive Behaviour ◽  
Extinction Learning ◽  
Behavioural Treatment ◽  
Related Pathway ◽  
Time Point

Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.

scholarly journals Dopaminergic signals in the Nucleus Accumbens, VTA and vmPFC underpin extinction learning from omitted threats

2020 ◽  
Author(s):  
Roland W Esser ◽  
Christoph Korn ◽  
Florian Ganzer ◽  
Jan Haaker
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Prediction Error ◽  
Computational Modelling ◽  
Extinction Learning ◽  
Behavioural Treatment ◽  
Dopaminergic Neurotransmission ◽  
Ventral Tegmental ◽  
Related Pathway

Learning to be safe is central to adjust behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and behavioural treatment of anxiety related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes absent but expected threats. We show that a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement (L-DOPA/Placebo) reduced retention of psychophysiological threat responses, which was mediated by activity in the ventromedial prefrontalcortex during extinction learning. L-DOPA administration enhanced signals at the timepoint of the omitted, but expected threat within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and amygdala. Computational modelling of threat expectancies further revealed prediction-error encoding in nucleus accumbens that was modulated by dopaminergic enhancement. Our results provide a mechanism to augment extinction learning by enhancement of dopaminergic neurotransmission that underlies encoding of absent threats.

scholarly journals Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex

2019 ◽  
Author(s):  
Emilie Werlen ◽  
Soon-Lim Shin ◽  
Francois Gastambide ◽  
Jennifer Francois ◽  
Mark D Tricklebank ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Orbitofrontal Cortex ◽  
Prediction Error ◽  
Learning Task ◽  
Adaptive Behaviour ◽  
Diagnostic Feature ◽  
Prediction Errors ◽  
Guided Learning ◽  
The Difference ◽  
Precise Relationship

AbstractIn an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events, and in the reward domain this has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear. To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC) while freely-moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats’ ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies using a proxy signal for BOLD in a freely behaving rodent.

scholarly journals Momentary subjective well-being depends on learning and not reward

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Bastien Blain ◽  
Robb B Rutledge
Keyword(s):  
Prediction Error ◽  
Computational Modelling ◽  
Well Being ◽  
Learning Task ◽  
Adaptive Behaviour ◽  
Subjective Well Being ◽  
Reward Prediction Error ◽  
Reward Prediction ◽  
The Difference ◽  
Momentary Happiness

Subjective well-being or happiness is often associated with wealth. Recent studies suggest that momentary happiness is associated with reward prediction error, the difference between experienced and predicted reward, a key component of adaptive behaviour. We tested subjects in a reinforcement learning task in which reward size and probability were uncorrelated, allowing us to dissociate between the contributions of reward and learning to happiness. Using computational modelling, we found convergent evidence across stable and volatile learning tasks that happiness, like behaviour, is sensitive to learning-relevant variables (i.e. probability prediction error). Unlike behaviour, happiness is not sensitive to learning-irrelevant variables (i.e. reward prediction error). Increasing volatility reduces how many past trials influence behaviour but not happiness. Finally, depressive symptoms reduce happiness more in volatile than stable environments. Our results suggest that how we learn about our world may be more important for how we feel than the rewards we actually receive.

scholarly journals Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex

2019 ◽  
Vol 45 (5) ◽  
pp. 793-803 ◽  
Author(s):  
Emilie Werlen ◽  
Soon-Lim Shin ◽  
Francois Gastambide ◽  
Jennifer Francois ◽  
Mark D. Tricklebank ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Orbitofrontal Cortex ◽  
Prediction Error ◽  
Learning Task ◽  
Adaptive Behaviour ◽  
Diagnostic Feature ◽  
Prediction Errors ◽  
Guided Learning ◽  
The Difference ◽  
Precise Relationship

Abstract In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events and in the reward domain that has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear. To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC), while freely moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats’ ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies by using a proxy signal for BOLD in a freely behaving rodent.

scholarly journals Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior

2012 ◽  
Vol 109 (28) ◽  
pp. 11360-11365 ◽  
Author(s):  
J. L. Warner-Schmidt ◽  
E. F. Schmidt ◽  
J. J. Marshall ◽  
A. J. Rubin ◽  
M. Arango-Lievano ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Cholinergic Interneurons

scholarly journals Stress decreases serotonin tone in the nucleus accumbens to promote aversion and potentiate cocaine preference via decreased stimulation of 5-HT1B receptors

2021 ◽  
Author(s):  
Harrison M Fontaine ◽  
Phillip R Silva ◽  
Carlie Neiswanger ◽  
Rachelle Tran ◽  
Antony D Abraham ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Indirect Pathway ◽  
Lateral Aspect ◽  
Drug Reward ◽  
Cholinergic Interneurons ◽  
Medial Nucleus ◽  
Conditional Deletion ◽  
Pharmacological Blockade ◽  
Monoaminergic Neurons ◽  
Stimulation Of

Stress-induced release of dynorphins (Dyn) activates kappa opioid receptors (KOR) in monoaminergic neurons to produce dysphoria and potentiate drug reward; however, the circuit mechanisms responsible for this effect are not known. We found that conditional deletion of KOR from Slc6a4 (SERT)-expressing neurons blocked stress-induced potentiation of cocaine conditioned place preference (CPP). Within the dorsal raphe nucleus (DRN), two overlapping populations of KOR-expressing neurons: Slc17a8 (VGluT3) and SERT, were distinguished functionally and anatomically. Optogenetic inhibition of these SERT+ neurons potentiated subsequent cocaine CPP, whereas optical inhibition of the VGluT3+ neurons blocked subsequent cocaine CPP. SERT+/VGluT3- expressing neurons were concentrated in the lateral aspect of the DRN. SERT projections from the DRN were observed in the medial nucleus accumbens (mNAc), but VGluT3 projections were not. Optical inhibition of SERT+ neurons produced place aversion, whereas optical stimulation of SERT+ terminals in the mNAc attenuated stress-induced increases in forced swim immobility and subsequent cocaine CPP. KOR neurons projecting to mNAc were confined to the lateral aspect of the DRN, and the principal source of dynorphinergic (Pdyn) afferents in the mNAc was from local neurons. Excision of Pdyn from the mNAc blocked stress-potentiation of cocaine CPP. Prior studies suggested that stress-induced dynorphin release within the mNAc activates KOR to potentiate cocaine preference by a reduction in 5-HT tone. Consistent with this hypothesis, a transient pharmacological blockade of mNAc 5-HT1B receptors potentiated subsequent cocaine CPP. 5-HT1B is known to be expressed on 5-HT terminals in NAc, and 5-HT1B transcript was also detected in Pdyn+, Adora2a+ and ChAT+ (markers for direct pathway, indirect pathway, and cholinergic interneurons, respectively). Following stress exposure, 5-HT1B transcript was selectively elevated in Pdyn+ cells of the mNAc. These findings suggest that Dyn/KOR regulates serotonin activation of 5HT1B receptors within the mNAc and dynamically controls stress response, affect, and drug reward.

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