Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.

Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and p...

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Main Authors: Frederique Chaperon, Markus Fendt, Peter H Kelly, Kurt Lingenhoehl, Johannes Mosbacher, Hans-Rudolf Olpe, Peter Schmid, Christine Sturchler, Kevin H McAllister, P Herman van der Putten, Christine E Gee
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3324554?pdf=render
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author Frederique Chaperon
Markus Fendt
Peter H Kelly
Kurt Lingenhoehl
Johannes Mosbacher
Hans-Rudolf Olpe
Peter Schmid
Christine Sturchler
Kevin H McAllister
P Herman van der Putten
Christine E Gee
author_facet Frederique Chaperon
Markus Fendt
Peter H Kelly
Kurt Lingenhoehl
Johannes Mosbacher
Hans-Rudolf Olpe
Peter Schmid
Christine Sturchler
Kevin H McAllister
P Herman van der Putten
Christine E Gee
author_sort Frederique Chaperon
collection DOAJ
description Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe(6), Leu-NHEt(13), des-Met(14))-Bombesin (6-14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders.
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spelling doaj.art-354b10421eb1418bbc11936d8893865b2022-12-21T19:53:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3496310.1371/journal.pone.0034963Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.Frederique ChaperonMarkus FendtPeter H KellyKurt LingenhoehlJohannes MosbacherHans-Rudolf OlpePeter SchmidChristine SturchlerKevin H McAllisterP Herman van der PuttenChristine E GeeLinks between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe(6), Leu-NHEt(13), des-Met(14))-Bombesin (6-14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders.http://europepmc.org/articles/PMC3324554?pdf=render
spellingShingle Frederique Chaperon
Markus Fendt
Peter H Kelly
Kurt Lingenhoehl
Johannes Mosbacher
Hans-Rudolf Olpe
Peter Schmid
Christine Sturchler
Kevin H McAllister
P Herman van der Putten
Christine E Gee
Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
PLoS ONE
title Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
title_full Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
title_fullStr Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
title_full_unstemmed Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
title_short Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.
title_sort gastrin releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory
url http://europepmc.org/articles/PMC3324554?pdf=render
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