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

• Published in: The Journal of neuroscience 2020-11, Vol.40 (47), p.9043-9054
• Main Authors: Giovanniello, Jacqueline, Yu, Kai, Furlan, Alessandro, Nachtrab, Gregory Thomas, Sharma, Radhashree, Chen, Xiaoke, Li, Bo
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Amygdala; Animal behavior; Animals; Central Amygdaloid Nucleus - drug effects; Central Amygdaloid Nucleus - physiology; Circuits; Conditioning (learning); Conditioning, Classical - drug effects; Conditioning, Classical - physiology; Defensive behavior; Fear; Fear - drug effects; Fear - physiology; Fear - psychology; Fear conditioning; Female; Globus pallidus; Globus Pallidus - drug effects; Globus Pallidus - physiology; Hybridization; Inactivation; Learning; Learning - physiology; Male; Mice; Mice, Inbred C57BL; Nerve Net - drug effects; Nerve Net - physiology; Neurons; Optogenetics; Photometry; Somatostatin; Somatostatin - biosynthesis; Somatostatin - genetics; Tetanus; Tetanus toxin; Tetanus Toxin - pharmacology; Toxins; Unconditioned stimulus
• ISSN: 0270-6474; 1529-2401
• 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, 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. 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. 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.