ORCID Profile
0000-0002-9342-7411
Current Organisation
Texas A&M University
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Publisher: Springer Science and Business Media LLC
Date: 02-09-2022
DOI: 10.1038/S41386-022-01427-W
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.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2018
Publisher: Society for Neuroscience
Date: 23-11-2011
DOI: 10.1523/JNEUROSCI.4095-11.2011
Abstract: Knowing when and where to express fear is essential to survival. Recent work in fear extinction paradigms reveals that the contextual regulation of fear involves a neural network involving the hippoc us, medial prefrontal cortex, and amygdala. The amygdaloid basal nuclei (BA) receive convergent input from the ventral hippoc us (VH) and prelimbic (PL) prefrontal cortex and may integrate VH and PL input to regulate fear expression. To examine the functional organization of this neural circuit, we used cellular imaging of c-fos expression in anatomically defined neuronal populations and circuit disconnections to identify the pathways involved in the contextual control of extinguished fear. Before behavioral testing, we infused a retrograde tracer into the amygdala to label BA-projecting neurons in VH and PL. Rats then underwent fear conditioning and extinction and were tested for their fear to the extinguished conditioned stimulus (CS) in either the extinction context or in another context freezing behavior served as the index of conditional fear. CS presentation outside the extinction context renewed conditional freezing and was associated with significantly more c-fos expression in BA-projecting neurons in the VH and PL than that induced by CS presentation in the extinction context. We next examined whether direct or indirect projections of VH to BA mediate fear renewal. Interestingly, disconnections of the VH from either the BA or PL eliminated renewal. These findings suggest that convergent inputs from both the VH and PL in the BA mediate the contextual control of fear after extinction.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.BIOPSYCH.2005.12.015
Abstract: Extinction depends, at least partly, on new learning that is specific to the context in which it is learned. Several behavioral phenomena (renewal, reinstatement, spontaneous recovery, and rapid reacquisition) suggest the importance of context in extinction. The present article reviews research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval. Contexts appear to select or retrieve the current relationship of the conditional stimulus (CS) with the unconditional stimulus (US), and they are provided by physical background cues, interoceptive drug cues, emotions, recent trials, and the passage of time. The current article pays particular attention to the effects of recent trials and trial spacing. Control of fear extinction by physical context involves interactions between the dorsal hippoc us and the lateral nucleus of the amygdala. This interaction may be mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2018
DOI: 10.1038/S41593-018-0183-4
Abstract: In the version of this article initially published, the traces in Fig. 1j and in Fig. 1k, right, were duplicated from the corresponding traces in Fig. 1c, bottom, and Fig. 1d, bottom right. The error has been corrected in the HTML and PDF versions of the article.
Location: United States of America
Location: United States of America
No related grants have been discovered for Stephen Maren.