Distinct Circuits from Central Lateral Amygdala to Ventral Part of Bed Nucleus of Stria Terminalis Regulate Different Fear Memory.

The ability to differentiate stimuli predicting fear is critical for survival, however, the underlying molecular and circuit mechanisms remain poorly understood.We combined transgenic mice, in vivo transsynaptic circuit-dissecting anatomical approaches, optogenetics, pharmacological methods and electrophysiological recording to investigate the involvement of specific extended amygdala circuits in different fear memory.We identify the projections from central lateral amygdala (CeL) protein kinase C δ (PKCδ) positive neurons and somatostatin (SST) positive neurons to the ventral part of bed nucleus of stria terminalis (vBNST) GABAergic and glutamatergic neurons. Prolonged optogenetic activation or inhibition of PKCδCeL-vBNST pathway specifically reduced context fear memory, whereas SSTCeL-vBNST pathway mainly reduced tone fear memory. Intriguingly, optogenetic manipulation of vBNST neurons received the projection from PKCδCeL exerted bidirectional regulation of context fear, whereas manipulation of vBNST neurons received the projection from SSTCeL neurons could bidirectionally regulate both context and tone fear memory. We subsequently demonstrated the presence of δ and κ opioid receptor protein expression within the CeL-vBNST circuits, potentially accounting for the discrepancy between prolonged activation of GABAergic circuits and inhibition of downstream vBNST neurons. Finally, administration of an opioid receptor antagonist cocktail on the PKCδCeL-vBNST or SSTCeL-vBNST pathway successfully restored context or tone fear memory reduction induced by prolonged activation of the circuits.Together, these findings establish a functional role for distinct CeL-vBNST circuits in the differential regulation and appropriate maintenance of fear.Copyright © 2023. Published by Elsevier Inc.

Citation

Yi Zhu, Shi-Ze Xie, Ai-Bing Peng, Xiao-Dan Yu, Chun-Yue Li, Jia-Yu Fu, Chen-Jie Shen, Shu-Xia Cao, Ying Zhang, Jiadong Chen, Xiao-Ming Li. Distinct Circuits from Central Lateral Amygdala to Ventral Part of Bed Nucleus of Stria Terminalis Regulate Different Fear Memory. Biological psychiatry. 2023 Sep 05

PMID: 37678543

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