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dc.contributor.authorZikopoulos, Basilisen_US
dc.contributor.authorHöistad, Malinen_US
dc.contributor.authorJohn, Yohanen_US
dc.contributor.authorBarbas, Helenen_US
dc.date.accessioned2021-11-24T20:41:06Z
dc.date.available2021-11-24T20:41:06Z
dc.date.issued2017-05-17
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000402804000003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654
dc.identifier.citationB. Zikopoulos, M. Hoistad, Y. John, H. Barbas. 2017. "Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions." JOURNAL OF NEUROSCIENCE, Volume 37, Issue 20, pp. 5051 - 5064. https://doi.org/10.1523/JNEUROSCI.3940-16.2017
dc.identifier.issn0270-6474
dc.identifier.urihttps://hdl.handle.net/2144/43416
dc.description.abstractThe bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive–emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders.en_US
dc.description.sponsorshipThis work was supported by NIH grants from NIMH and NINDS. We thank Drs. Paul Greengard and Jean-Antoine Girault for the gift of the DARPP-32 antibody, Dr. John Fiala for assistance in adapting the free 3D-reconstruction software he developed, Dr. Angela Carville for veterinary care, and Linda Fernsten for surgical assistance. (NIH grant from NIMH; NIH grant from NINDS)en_US
dc.format.extentpp. 5051 - 5064en_US
dc.languageEnglish
dc.language.isoen_US
dc.publisherSOC NEUROSCIENCEen_US
dc.relation.ispartofJOURNAL OF NEUROSCIENCE
dc.rightsCopyright © 2017 the authors. This work is available to the public to copy, distribute, or display under the terms of the Creative Commons Attribution 4.0 International License (CC-BY). This license allows data and text mining, use of figures in presentations, and posting the article online, provided that the original article is credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titlePosterior orbitofrontal and anterior cingulate pathways to the amygdala target inhibitory and excitatory systems with opposite functionsen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1523/JNEUROSCI.3940-16.2017
pubs.elements-sourceweb-of-scienceen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent Collegeen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent College, Health Sciencesen_US
pubs.publication-statusPublisheden_US
dc.identifier.mycv193555


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Copyright © 2017 the authors. This work is available to the public to copy, distribute, or display under the terms of the Creative Commons Attribution 4.0 International License (CC-BY). This license allows data and text mining, use of figures in presentations, and posting the article online, provided that the original article is credited.
Except where otherwise noted, this item's license is described as Copyright © 2017 the authors. This work is available to the public to copy, distribute, or display under the terms of the Creative Commons Attribution 4.0 International License (CC-BY). This license allows data and text mining, use of figures in presentations, and posting the article online, provided that the original article is credited.