title: μ-Opioid Receptor-Mediated Inhibition of Intercalated Neurons and Effect on Synaptic Transmission to the Central Amygdala.
abstract: The amygdala is a key region for the processing of information underlying fear, anxiety, and fear extinction. Within the local neuronal networks of the amygdala, a population of inhibitory, intercalated neurons (ITCs) modulates the flow of information among various nuclei of amygdala, including the basal nucleus (BA) and the centromedial nucleus (CeM) of the amygdala. These ITCs have been shown to be important during fear extinction and are target of a variety of neurotransmitters and neuropeptides. Here we provide evidence that the activation of μ-opioid receptors (MORs) by the specific agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin) hyperpolarizes medially located ITCs (mITCs) in acute brain slices of mice. Moreover, we use whole-cell patch-clamp recordings in combination with local electrical stimulation or glutamate uncaging to analyze the effect of MOR activation on local microcircuits. We show that the GABAergic transmission between mITCs and CeM neurons is attenuated by DAMGO, whereas the glutamatergic transmission on CeM neurons and mITCs is unaffected. Furthermore, MOR activation induced by theta burst stimulation in BA suppresses plastic changes of feedforward inhibitory transmission onto CeM neurons as revealed by the MOR antagonist CTAP d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2. In summary, the mITCs constitute a target for the opioid system, and therefore, the activation of MOR in ITCs might play a central role in the modulation of the information processing between the basolateral complex of the amygdala and central nuclei of the amygdala.
authors.affiliation: Institute of Physiology I, University of Münster, D-48149 Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Blaesse
authors.affiliation: Institute of Physiology I, University of Münster, D-48149 Münster, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Goedecke
authors.affiliation: MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, OX1 3TH, United Kingdom, and GW Pharmaceuticals, School of Chemistry, Food and Nutritional Science and Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, United Kingdom.
authors.forename: Michaël
authors.initials: M
authors.lastname: Bazelot
authors.affiliation: MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, OX1 3TH, United Kingdom, and.
authors.forename: Marco
authors.identifier: http://orcid.org/0000-0002-2742-5485
authors.initials: M
authors.lastname: Capogna
authors.affiliation: Institute of Physiology I, University of Münster, D-48149 Münster, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.affiliation: Institute of Physiology I, University of Münster, D-48149 Münster, Germany, Kay.Juengling@gmx.de.
authors.forename: Kay
authors.identifier: http://orcid.org/0000-0001-9639-8815
authors.initials: K
authors.lastname: Jüngling
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000166:cytology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D010455:Peptides; D011810:Quinoxalines; D017450:Receptors, Opioid, mu; D026941:Sodium Channel Blockers; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D013779:Tetrodotoxin; C056723:FG 9041; C009862:connective tissue-activating peptide; C056639:2-amino-5-phosphopentanoic acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D014633:Valine
keywords: MOR; central amygdala; opioids; plasticity