A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning

Giovanniello, J., Yu, K., Furlan, A., Nachtrab, G. T., Sharma, R., Chen, X., Li, B. (November 2020) A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning. J Neurosci, 40 (47). pp. 9043-9054. ISSN 0270-6474 (Print)0270-6474

URL: https://pubmed.ncbi.nlm.nih.gov/33067362/
DOI: 10.1523/jneurosci.2090-20.2020


The central amygdala (CeA) is critically involved in a range of adaptive behaviors, including defensive behaviors. Neurons in the CeA send long-range projections to a number of extra-amygdala targets, but the functions of these projections remain elusive. Here, we report that a previously neglected CeA-to-globus pallidus external segment (GPe) circuit plays an essential role in classical fear conditioning. By anatomic tracing, in situ hybridization and channelrhodopsin (ChR2)-assisted circuit mapping in both male and female mice, we found that a subset of CeA neurons send projections to the GPe, and the majority of these GPe-projecting CeA neurons express the neuropeptide somatostatin. Notably, chronic inhibition of GPe-projecting CeA neurons with the tetanus toxin light chain (TeLC) completely blocks auditory fear conditioning. In vivo fiber photometry revealed that these neurons are selectively excited by the unconditioned stimulus (US) during fear conditioning. Furthermore, transient optogenetic inactivation or activation of these neurons selectively during US presentation impairs or promotes, respectively, fear learning. Our results suggest that a major function of GPe-projecting CeA neurons is to represent and convey US-related information through the CeA-GPe circuit, thereby regulating learning in fear conditioning.SIGNIFICANCE STATEMENT The central amygdala (CeA) has been implicated in the establishment of defensive behaviors toward threats, but the underlying circuit mechanisms remain unclear. Here, we found that a subpopulation of neurons in the CeA, which are mainly those that express the neuropeptide somatostatin, send projections to the globus pallidus external segment (GPe), and this CeA-GPe circuit conveys unconditioned stimulus (US)-related information during classical fear conditioning, thereby having an indispensable role in learning. Our results reveal a previously unknown circuit mechanism for fear learning.

Item Type: Paper
Additional Information: 1529-2401 Giovanniello, Jacqueline Orcid: 0000-0002-4558-7728 Yu, Kai Orcid: 0000-0003-1481-1288 Furlan, Alessandro Nachtrab, Gregory Thomas Sharma, Radhashree Chen, Xiaoke Li, Bo Orcid: 0000-0002-0154-3088 R01 MH101214/MH/NIMH NIH HHS/United States R01 MH108924/MH/NIMH NIH HHS/United States R01 NS104944/NS/NINDS NIH HHS/United States T32 GM065094/GM/NIGMS NIH HHS/United States Journal Article J Neurosci. 2020 Nov 18;40(47):9043-9054. doi: 10.1523/JNEUROSCI.2090-20.2020. Epub 2020 Oct 16.
Uncontrolled Keywords: central amygdala fear conditioning globus pallidus learning somatostatin unconditioned stimulus
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > amygdala
organism description > animal
organism description > animal behavior
organism description > animal behavior > fear
organism description > animal behavior > learning
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
organism description > animal > mammal > rodent
CSHL Authors:
Communities: CSHL labs > Li lab
School of Biological Sciences > Publications
Depositing User: Matthew Dunn
Date: 18 November 2020
Date Deposited: 19 Feb 2021 20:47
Last Modified: 30 Jan 2024 20:44
PMCID: PMC7673004
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39859

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