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 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 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 Insulin in the ventral tegmental area reduces cocaine‐evoked dopamine in the nucleus accumbens in vivo

2018 ◽  
Vol 50 (3) ◽  
pp. 2146-2155 ◽  
Author(s):  
Lindsay Naef ◽  
Lauren Seabrook ◽  
Jeff Hsiao ◽  
Calvin Li ◽  
Stephanie L. Borgland
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Ventral Tegmental

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.

Sign in / Sign up

Export Citation Format

Share Document