scholarly journals Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ayla Aksoy-Aksel ◽  
Andrea Gall ◽  
Anna Seewald ◽  
Francesco Ferraguti ◽  
Ingrid Ehrlich
Keyword(s):  
Prediction Error ◽  
D1 Receptors ◽  
Male Mice ◽  
Direct Inhibition ◽  
Extinction Learning ◽  
Intercalated Cell ◽  
Midbrain Neurons ◽  
Dopaminergic Mechanisms ◽  
Inhibitory Interactions ◽  
Fear Behavior

Dopaminergic signaling plays an important role in associative learning, including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive one of the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct novel mechanisms by which mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1 receptors. Early extinction training augments both GABA co-release onto dorsomedial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.

scholarly journals Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms

2020 ◽  
Author(s):  
Ayla Aksoy-Aksel ◽  
Andrea Gall ◽  
Anna Seewald ◽  
Francesco Ferraguti ◽  
Ingrid Ehrlich
Keyword(s):  
Associative Learning ◽  
Prediction Error ◽  
D1 Receptors ◽  
Direct Inhibition ◽  
Extinction Learning ◽  
Intercalated Cell ◽  
Midbrain Neurons ◽  
Dopaminergic Mechanisms ◽  
Inhibitory Interactions ◽  
Fear Behavior

AbstractDopaminergic signaling plays an important role in associative learning including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial cluster ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct mechanisms how mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1-receptors. Early extinction training augments both, GABA co-release onto dorso-medial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.

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.

Dopamine neurons coding prediction errors in reward space, but not in aversive space: a matter of location?

2014 ◽  
Vol 112 (5) ◽  
pp. 1021-1024 ◽  
Author(s):  
Joachim Morrens
Keyword(s):  
Prediction Error ◽  
Dopamine Neurons ◽  
Prediction Errors ◽  
Neurotransmitter Systems ◽  
Aversive Stimuli ◽  
Midbrain Neurons ◽  
Appetitive Stimuli ◽  
Error Coding ◽  
Potential Issue

Dopamine midbrain neurons are well known for prediction error coding in a reward context. A recent report by Christopher Fiorillo ( Science 341: 546–549, 2013), however, suggests that these neurons behave markedly different when subjects get confronted with aversive, rather than appetitive, stimuli. Despite his findings being in line with indications of appetitive and aversive stimuli being processed by distinct neurotransmitter systems, they should still be interpreted with some caution due to a potential issue of recording location.

scholarly journals Trial-by-trial dynamics of reward prediction error-associated signals during extinction learning and renewal

2020 ◽  
pp. 101901
Author(s):  
Julian Packheiser ◽  
José R. Donoso ◽  
Sen Cheng ◽  
Onur Güntürkün ◽  
Roland Pusch
Keyword(s):  
Prediction Error ◽  
Extinction Learning ◽  
Reward Prediction Error ◽  
Reward Prediction

scholarly journals A ventral striatal prediction error signal in human fear extinction learning

NeuroImage ◽  
2021 ◽  
Vol 229 ◽  
pp. 117709 ◽  
Author(s):  
M. Thiele ◽  
K.S.L. Yuen ◽  
A.V.M. Gerlicher ◽  
R. Kalisch
Keyword(s):  
Prediction Error ◽  
Fear Extinction ◽  
Error Signal ◽  
Extinction Learning

scholarly journals Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jimena Laura Frontera ◽  
Hind Baba Aissa ◽  
Romain William Sala ◽  
Caroline Mailhes-Hamon ◽  
Ioana Antoaneta Georgescu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Associative Learning ◽  
Prediction Error ◽  
Functional Role ◽  
Extinction Learning ◽  
Brain Areas ◽  
Periaqueductal Grey ◽  
Cerebellar Neurons ◽  
Emotional System

Abstract Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.

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.

Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

1970 ◽  
Vol 28 ◽  
pp. 208-209
Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA
Keyword(s):  
Osmium Tetroxide ◽  
Male Mice ◽  
Alcohol Group ◽  
Group Iii ◽  
Group I ◽  
C57bl Mice ◽  
Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

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