Dopamine induces fear extinction by activating the reward-responding amygdala neurons DOI Creative Commons
Xiangyu Zhang,

Katelyn Flick,

Marianna Rizzo

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(18)

Published: April 28, 2025

The extinction of conditioned fear responses is crucial for adaptive behavior, and its impairment a hallmark anxiety disorders such as posttraumatic stress disorder. Fear takes place when animals form new memory that suppresses the original memory. In case context-dependent memory, formed within reward-responding posterior subset basolateral amygdala (BLA) genetically marked by Ppp1r1b + neurons. These engram cells suppress activity fear-responding Rspo2 present in anterior BLA, hence extinction. However, neurological nature teaching signal instructs formation neurons unknown. Here, we demonstrate ventral tegmental area (VTA) dopaminergic signaling drives distinct BLA neuronal populations. We show populations receive topographically divergent inputs from VTA via differentially expressed dopamine receptors. Fiber photometry recordings reveal (DA) time-locked to freezing cessation neurons, but not Furthermore, this correlates with learning. Finally, using projection-specific optogenetic manipulation, find activation DA projections reward accelerated or impaired extinction, respectively. Together, work demonstrates bidirectionally controls patterns at

Language: Английский

Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons DOI Creative Commons
Ana Verónica Domingues, Tawan T. A. Carvalho, Gabriela J. Martins

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

The nucleus accumbens (NAc) is a key brain region for motivated behaviors, yet how distinct neuronal populations encode appetitive or aversive stimuli remains undetermined. Using microendoscopic calcium imaging in mice, we tracked NAc shell D1- D2-medium spiny neurons' (MSNs) activity during exposure to of opposing valence and associative learning. Despite drift individual coding, both D2-population was sufficient discriminate unconditioned stimuli, but not predictive cues. Notably, D2-MSNs were similarly co-recruited conditioning, supporting concurrent role Conversely, when contingencies changed, there an asymmetric response the NAc, with more pronounced changes D2-MSNs. Optogenetic manipulation provided causal evidence necessity this population extinction associations. Our results reveal neurons valence, Pavlovian associations their extinction, unveil mechanisms underlying behaviors. rewarding Here, authors show that appeared be relevant

Language: Английский

Citations

2
Sex differences in fear extinction DOI
Eric Raúl Velasco, Antonio Florido, Mohammed R. Milad

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2019, Volume and Issue: 103, P. 81 - 108

Published: May 23, 2019

Language: Английский

Citations

104
Intercalated amygdala clusters orchestrate a switch in fear state DOI
Kenta M. Hagihara, Olena Bukalo,

Martin Zeller

et al.

Nature, Journal Year: 2021, Volume and Issue: 594(7863), P. 403 - 407

Published: May 26, 2021

Language: Английский

Citations

101
A Dopaminergic Basis for Fear Extinction DOI
Raffaël Kalisch, Anna Gerlicher, Sevil Duvarci

et al.

Trends in Cognitive Sciences, Journal Year: 2019, Volume and Issue: 23(4), P. 274 - 277

Published: Feb. 23, 2019

Language: Английский

Citations

100
Dopamine Neurons Reflect the Uncertainty in Fear Generalization DOI Creative Commons
Yong Sang Jo, Gabriel Heymann, Larry S. Zweifel

et al.

Neuron, Journal Year: 2018, Volume and Issue: 100(4), P. 916 - 925.e3

Published: Oct. 11, 2018

Language: Английский

Citations

98
Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times DOI Creative Commons
Lili Cai,

Katherine Pizano,

Gregory W. Gundersen

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: June 10, 2020

Dopamine (DA) neurons are to encode reward prediction error (RPE), in addition other signals, such as salience. While RPE is known support learning, the role of salience learning remains less clear. To address this, we recorded and manipulated VTA DA mice during fear extinction. We applied deep classify mouse freezing behavior, eliminating need for human scoring. Our fiber photometry recordings showed medial lateral have distinct activity profiles extinction: more closely reflected RPE, while a salience-like signal. Optogenetic inhibition either region slowed extinction, with relevant time period differing across regions. results indicate signals can similar downstream consequences RPE-like although different temporal dependencies.

Language: Английский

Citations

96
Aversion hot spots in the dopamine system DOI
Jeroen P. H. Verharen, Yichen Zhu, Stephan Lammel

et al.

Current Opinion in Neurobiology, Journal Year: 2020, Volume and Issue: 64, P. 46 - 52

Published: March 9, 2020

Language: Английский

Citations

76
Neural Circuits Underlying Behavioral Flexibility: Insights From Drosophila DOI Creative Commons
Anita V. Devineni, Kristin M. Scaplen

Frontiers in Behavioral Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 6, 2022

Behavioral flexibility is critical to survival. Animals must adapt their behavioral responses based on changes in the environmental context, internal state, or experience. Studies Drosophila melanogaster have provided insight into neural circuit mechanisms underlying flexibility. Here we discuss how behavior modulated by and learning. We describe general principles of organization modulation that underlie flexibility, are likely extend other species.

Language: Английский

Citations

41
Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways DOI Creative Commons
Qi Wang,

Jia‐Jie Zhu,

Lizhao Wang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 21, 2022

Abstract Threat and extinction memories are crucial for organisms’ survival in changing environments. These believed to be encoded by separate ensembles of neurons the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning paradigm male mice, here we discovered that two distinct projection neuron subpopulations physical proximity within insular cortex (IC), targeting central amygdala (CeA) nucleus accumbens (NAc), respectively, encode fear memories. Reciprocal intracortical inhibition these IC gates emergence either or memory. rabies-virus-assisted tracing, found IC-NAc preferentially innervated intercortical inputs from orbitofrontal (OFC), specifically enhancing override results demonstrate serves as operation node harboring decipher memory under top-down executive control OFC.

Language: Английский

Citations

40
A cortico-amygdala neural substrate for endocannabinoid modulation of fear extinction DOI
Ozge Gunduz‐Cinar,

Laura I. Castillo,

Maya Xia

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(19), P. 3053 - 3067.e10

Published: July 21, 2023

Language: Английский

Citations

29