@article{285640f3d7b94b359948e9b1c290fddc,
title = "Basal forebrain cholinergic signaling in the basolateral amygdala promotes strength and durability of fear memories",
abstract = "The basolateral amygdala (BLA) complex receives dense cholinergic projections from the nucleus basalis of Meynert (NBM) and the horizontal limb of the diagonal band of Broca (HDB). The present experiments examined whether these projections regulate the formation, extinction, and renewal of fear memories. This was achieved by employing a Pavlovian fear conditioning protocol and optogenetics in transgenic rats. Silencing NBM projections during fear conditioning weakened the fear memory produced by that conditioning and abolished its renewal after extinction. By contrast, silencing HDB projections during fear conditioning had no effect. Silencing NBM or HDB projections during extinction enhanced the loss of fear produced by extinction, but only HDB silencing prevented renewal. Next, we found that systemic blockade of nicotinic acetylcholine receptors during fear conditioning mimicked the effects produced by silencing NBM projections during fear conditioning. However, this blockade had no effect when given during extinction. These findings indicate that basal forebrain cholinergic signaling in the BLA plays a critical role in fear regulation by promoting strength and durability of fear memories. We concluded that cholinergic compounds may improve treatments for post-traumatic stress disorder by durably stripping fear memories from their fear-eliciting capacity.",
author = "Crimmins, \{Byron E.\} and Lingawi, \{Nura W.\} and Chieng, \{Billy C.\} and Leung, \{Beatrice K.\} and Stephen Maren and Vincent Laurent",
note = "This work was supported by the National Health and Medical Research of Australia in the form of an Ideas grant (APP2003686) to NWL, BKL, and VL and the Faculty of Science at University of New South Wales (Silverstar Award). Open Access funding enabled and organized by CAUL and its Member Institutions. Considerable research effort has been deployed to describe the psychological and neural mechanisms underlying fear regulation [–]. The present study used optogenetics and pharmacological methods to examine how basal forebrain cholinergic projections to the BLA influence the formation, extinction, and renewal of fear memories. We revealed for the first time that these projections control the strength and durability of fear memories. This control was implemented by NBM cholinergic projections during fear memory formation and was supported by HDB cholinergic projections during extinction. Removing either form of cholinergic control produced a fear memory that lost its fear-eliciting capacity faster following extinction and that was unable to trigger fear again despite context shifts. We also gathered evidence suggesting that NBM-mediated control involved nAchR activation during fear memory formation whereas HDB-mediated control during extinction did not recruit these receptors. Together, these findings underscore the critical role played BLA cholinergic signaling in fear regulation.",
year = "2023",
month = mar,
doi = "10.1038/s41386-022-01427-w",
language = "English (US)",
volume = "48",
pages = "605--614",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Springer Nature",
number = "4",
}