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杏仁核奖励神经元形成并存储恐惧消退记忆。

Amygdala Reward Neurons Form and Store Fear Extinction Memory.

机构信息

RIKEN-MIT Laboratory for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

RIKEN-MIT Laboratory for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Neuron. 2020 Mar 18;105(6):1077-1093.e7. doi: 10.1016/j.neuron.2019.12.025. Epub 2020 Jan 14.


DOI:10.1016/j.neuron.2019.12.025
PMID:31952856
Abstract

The ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of this new extinction memory. Here we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drives reward behaviors and antagonizes the BLA's original fear neurons. Activation of fear extinction engram neurons and natural reward-responsive neurons overlap significantly in the BLA. Furthermore, these two neuronal subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory. VIDEO ABSTRACT.

摘要

消除条件性恐惧记忆的能力对于恐惧反应的适应性控制至关重要,而其损伤是创伤后应激障碍(PTSD)等情绪障碍的标志。当动物形成一种新的记忆来抑制原始的恐惧记忆时,就被认为发生了恐惧的消除。然而,对于这种新的遗忘记忆的性质和形成及储存的部位却知之甚少。在这里,我们证明了恐惧遗忘记忆印记是在一个基因上不同的基底外侧杏仁核(BLA)神经元群体中形成和储存的,该群体驱动奖励行为,并拮抗 BLA 中原始的恐惧神经元。BLA 中恐惧遗忘记忆印记神经元和自然奖赏反应神经元的激活有很大的重叠。此外,这两个神经元亚群在驱动奖励行为和恐惧消除行为方面是可以相互替换的。因此,恐惧消除记忆是一种新形成的奖励记忆。视频摘要。

相似文献

[1]
Amygdala Reward Neurons Form and Store Fear Extinction Memory.

Neuron. 2020-1-14

[2]
Bidirectional switch of the valence associated with a hippocampal contextual memory engram.

Nature. 2014-9-18

[3]
Pharmacogenetic reactivation of the original engram evokes an extinguished fear memory.

Neuropharmacology. 2017-2

[4]
Dynamic tripartite construct of interregional engram circuits underlies forgetting of extinction memory.

Mol Psychiatry. 2022-10

[5]
Synaptic encoding of fear extinction in mPFC-amygdala circuits.

Neuron. 2013-11-27

[6]
Distinct engrams control fear and extinction memory.

Hippocampus. 2024-5

[7]
Opto-extinction of a threat memory in mice.

Brain Res Bull. 2022-12

[8]
Distinct hippocampal engrams control extinction and relapse of fear memory.

Nat Neurosci. 2019-4-1

[9]
Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex.

Nat Neurosci. 2017-3-13

[10]
Dendritic structural plasticity in the basolateral amygdala after fear conditioning and its extinction in mice.

Behav Brain Res. 2013-4-6

引用本文的文献

[1]
Combinative Protein Expression of Immediate Early Genes c-Fos, Arc, and Npas4 Along Aversive and Appetitive Experience-Related Neural Networks.

Hippocampus. 2025-9

[2]
Representational dynamics during extinction of fear memories in the human brain.

Nat Hum Behav. 2025-8-5

[3]
Stress-responsive neuronal ensembles and β-adrenergic signaling in the basolateral amygdala modulate the infra-limbic cortical activity and govern the delayed stress-induced fear extinction deficit.

J Neurosci. 2025-7-7

[4]
Chronic postoperative pain induces contextual fear extinction dysfunction through hippocampal NMDAR/BDNF/TrkB signaling pathway in mice.

Transl Psychiatry. 2025-6-17

[5]
Directing negative emotional states through parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions.

Mol Psychiatry. 2025-6-13

[6]
Ventral hippocampus neurons encode meal-related memory.

Nat Commun. 2025-6-11

[7]
Combinative protein expression of immediate early genes c-Fos, Arc, and Npas4 along aversive- and reward-related neural networks.

bioRxiv. 2025-5-22

[8]
Stellate ganglion block diminishes consolidation of conditioned fear memory in mice by inhibiting the locus coeruleus to the basolateral amygdala neural circuit.

Transl Psychiatry. 2025-5-17

[9]
[4‑(Arylethyl)‑pyrrolo[2,3-d] pyrimidine improves post-traumatic stress disorder in mice by inhibiting mGluR5-regulated ERK1/2-SGK1 signaling pathway].

Nan Fang Yi Ke Da Xue Xue Bao. 2025-4-20

[10]
Dopamine induces fear extinction by activating the reward-responding amygdala neurons.

Proc Natl Acad Sci U S A. 2025-5-6

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