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      • Record: found
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      Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations

      brief-report

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          Abstract

          Background

          Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated.

          Methods

          We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation.

          Results

          Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala.

          Conclusions

          These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867.

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          Most cited references22

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          Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear.

          Demetrio Sierra-Mercado, Gregory J. Quirk, Nancy Padilla-Coreano (2011)
          Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. Moreover, it is the ventral HPC (vHPC), rather than the dorsal HPC, that projects to vmPFC and BLA. To help determine regional specificity, we used small doses of the GABA(A) agonist muscimol to selectively inactivate IL, PL, BLA, or vHPC in an auditory fear conditioning and extinction paradigm. Infusions were performed prior to extinction training, allowing us to assess the effects on both fear expression and subsequent extinction memory. Inactivation of IL had no effect on fear expression, but impaired the within-session acquisition of extinction as well as extinction memory. In contrast, inactivation of PL impaired fear expression, but had no effect on extinction memory. Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.
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            Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

            T Sakurai, A Amemiya, M Ishii … (1998)
            The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
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              The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

              L de Lecea, T S Kilduff, C Peyron … (1998)
              We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
              Article 0 comments Cited 345 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Neuropsychopharmacol
                Journal ID (iso-abbrev): Int. J. Neuropsychopharmacol
                Journal ID (publisher-id): ijnp
                Title: International Journal of Neuropsychopharmacology
                Publisher: Oxford University Press (US )
                ISSN (Print): 1461-1457
                ISSN (Electronic): 1469-5111
                Publication date Collection: August 2017
                Publication date (Electronic): 27 April 2017
                Publication date PMC-release: 27 April 2017
                Volume: 20
                Issue: 8
                Pages: 654-659
                Affiliations
                [1 ] Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra , Barcelona, Spain (Drs Flores, Maldonado, and Berrendero); INSERM, Neurocentre Magendie , Bordeaux, France (Dr Herry); University Bordeaux, Neurocentre Magendie , Bordeaux, France (Dr Herry); Faculty of Experimental Sciences, Universidad Francisco de Vitoria , Madrid, Spain (Dr Berrendero).
                Author notes

                Correspondence: Rafael Maldonado, MD, PhD, Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, C/ Doctor Aiguader 88, 08003 Barcelona, Spain ( rafael.maldonado@ 123456upf.edu ); and Fernando Berrendero, PhD, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarcón, Madrid, Spain ( fernando.berrendero@ 123456ufv.es ).

                Article
                Publisher ID: pyx029
                DOI: 10.1093/ijnp/pyx029
                PMC ID: 5570099
                PubMed ID: 28453642
                SO-VID: 69f2c68b-06be-407c-a0fe-ad15d1c74f92
                Copyright © © The Author 2017. Published by Oxford University Press on behalf of CINP.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Page count
                Pages: 6
                Funding
                Funded by: Instituto de Salud Carlos III 10.13039/501100004587
                Award ID: PI13/00042
                Categories
                Subject: Brief Report
                Subject: Editor's Choice

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: fear extinction,orexin,amygdala,retrograde labeling,calbindin
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: fear extinction, orexin, amygdala, retrograde labeling, calbindin

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