title: Large intercalated neurons of amygdala relay noxious sensory information.
abstract: Various GABAergic neuron types of the amygdala cooperate to control principal cell firing during fear-related and other behaviors, and understanding their specialized roles is important. Among GABAergic neurons, the so-called intercalated cells (ITCcs) are critically involved in the expression and extinction of fear memory. Tightly clustered small-sized spiny neurons constitute the majority of ITCcs, but they are surrounded by sparse, larger neurons (L-ITCcs) for which very little information is known. We report here a detailed neurochemical, structural and physiological characterization of rat L-ITCcs, as identified with juxtacellular recording/labeling in vivo. We supplement these data with anatomical and neurochemical analyses of nonrecorded L-ITCcs. We demonstrate that L-ITCcs are GABAergic, and strongly express metabotropic glutamate receptor 1α and GABAA receptor α1 subunit, together with moderate levels of parvalbumin. Furthermore, L-ITCcs are innervated by fibers enriched with metabotropic glutamate receptors 7a and/or 8a. In contrast to small-sized spiny ITCcs, L-ITCcs possess thick, aspiny dendrites, have highly branched, long-range axonal projections, and innervate interneurons in the basolateral amygdaloid complex. The axons of L-ITCcs also project to distant brain areas, such as the perirhinal, entorhinal, and endopiriform cortices. In vivo recorded L-ITCcs are strongly activated by noxious stimuli, such as hindpaw pinches or electrical footshocks. Consistent with this, we observed synaptic contacts on L-ITCc dendrites from nociceptive intralaminar thalamic nuclei. We propose that, during salient sensory stimulation, L-ITCcs disinhibit local and distant principal neurons, acting as "hub cells," to orchestrate the activity of a distributed network.
authors: Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, and.
authors: Thomas C M
authors: TC
authors: Bienvenu
authors: Department of Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
authors: Daniela
authors: D
authors: Busti
authors: Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, and.
authors: Benjamin R
authors: http://orcid.org/0000-0002-0315-6022
authors: BR
authors: Micklem
authors: Department of Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
authors: Mahnaz
authors: M
authors: Mansouri
authors: Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, and.
authors: Peter J
authors: PJ
authors: Magill
authors: Department of Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria marco.capogna@pharm.ox.ac.uk francesco.ferraguti@i-med.ac.at.
authors: Francesco
authors: F
authors: Ferraguti
authors: Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, United Kingdom, and marco.capogna@pharm.ox.ac.uk francesco.ferraguti@i-med.ac.at.
authors: Marco
authors: http://orcid.org/0000-0002-2742-5485
authors: M
authors: Capogna
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D018728:Entorhinal Cortex / Q000166:cytology / Q000502:physiology; D005073:Evoked Potentials, Somatosensory; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008297:Male; D059225:Nociception; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate
keywords: GABAergic neurons; amygdala; juxtacellular recording; metabotropic glutamate receptors; neuroanatomy; somatosensory stimulation
references: J Neurosci. 1997 Oct 1;17(19):7503-22
references: 9295396
references: J Neurosci. 2010 Nov 3;30(44):14610-8
references: 21048118
references: Physiol Rev. 2010 Apr;90(2):419-63
references: 20393190
references: Nat Neurosci. 2009 Dec;12(12):1586-93
references: 19898469
references: Eur J Neurosci. 2009 Jan;29(2):340-58
references: 19200238
references: Neuroscience. 1993 Jan;52(2):281-94
references: 8450947
references: Neuron. 2012 Apr 12;74(1):57-64
references: 22500630
references: Neuroscience. 2012 Feb 17;203:59-77
references: 22210508
references: J Comp Neurol. 1994 Sep 8;347(2):249-74
references: 7814667
references: Exp Brain Res. 2000 Oct;134(4):520-32
references: 11081834
references: Curr Opin Neurobiol. 2013 Jun;23(3):346-52
references: 23402950
references: Prog Neurobiol. 2004 Oct;74(2):101-10
references: 15518955
references: J Neurosci. 2011 Nov 23;31(47):16916-27
references: 22114262
references: J Neurosci. 1999 Dec 1;19(23):10575-83
references: 10575053
references: Nature. 2008 Jul 31;454(7204):642-5
references: 18615014
references: J Neurosci Methods. 1996 Apr;65(2):113-36
references: 8740589
references: Neuron. 2008 Jul 31;59(2):298-310
references: 18667157
references: J Comp Neurol. 2008 Dec 20;511(6):847-62
references: 18925632
references: Hippocampus. 2004;14(2):193-215
references: 15098725
references: J Comp Neurol. 1986 May 8;247(2):246-71
references: 2424941
references: Neuron. 2008 Mar 27;57(6):917-29
references: 18367092
references: Neuroscience. 2007 Oct 12;149(1):131-43
references: 17850980
references: PLoS One. 2008 Apr 16;3(4):e2004
references: 18414674
references: Neuropharmacology. 2013 Mar;66:274-89
references: 22643400
references: Eur J Neurosci. 2011 Mar;33(5):868-78
references: 21219474
references: J Neurosci. 2005 Nov 9;25(45):10520-36
references: 16280590
references: Neuron. 2012 Jun 21;74(6):1059-74
references: 22726836
references: Nat Rev Neurosci. 2012 Sep;13(9):651-8
references: 22850830
references: Eur J Neurosci. 1999 Oct;11(10):3441-8
references: 10564352
references: J Neurosci. 2007 Aug 1;27(31):8184-9
references: 17670965
references: Nat Neurosci. 2010 Apr;13(4):489-94
references: 20208529
references: J Neurosci Methods. 1980 Dec;3(2):129-49
references: 6110810
references: Curr Opin Neurobiol. 2014 Jun;26:51-6
references: 24650504
references: Neuroscience. 1993 Dec;57(4):1061-76
references: 8309543
references: J Physiol. 2007 Nov 15;585(Pt 1):117-34
references: 17916608
references: J Neurosci. 1996 May 15;16(10):3334-50
references: 8627370
references: Nature. 2003 Feb 20;421(6925):844-8
references: 12594513
references: J Physiol. 2011 Apr 15;589(Pt 8):1911-25
references: 21224220
references: Science. 2009 Dec 4;326(5958):1419-24
references: 19965761
references: Curr Opin Neurobiol. 2014 Jun;26:110-6
references: 24486420
references: J Comp Neurol. 2008 Jan 20;506(3):373-86
references: 18041776
references: J Recept Res. 1991;11(1-4):407-24
references: 1653345
references: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6726-30
references: 1323116
references: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13372-7
references: 11069288
references: J Neurosci. 2011 Mar 30;31(13):5131-44
references: 21451049
references: J Neurosci. 2010 Oct 13;30(41):13586-96
references: 20943900
references: Neuron. 2009 Jun 25;62(6):757-71
references: 19555645
references: J Neurophysiol. 2011 Jun;105(6):3054-66
references: 21471396
references: Neuron. 2005 Apr 7;46(1):141-51
references: 15820700
references: Neurobiol Learn Mem. 2014 Sep;113:82-9
references: 24091205
references: J Neurophysiol. 2000 Jun;83(6):3509-18
references: 10848566
references: Neuroscience. 2006;139(4):1479-93
references: 16516396
references: Neuroscience. 2001;102(3):527-40
references: 11226691
references: Eur J Neurosci. 2000 Mar;12(3):781-92
references: 10762307
references: Neuron. 2014 Jun 4;82(5):966-80
references: 24908482
references: Annu Rev Neurosci. 2000;23:155-84
references: 10845062
references: J Neurosci. 2011 Dec 7;31(49):18073-93
references: 22159120
references: J Neurochem. 1985 Nov;45(5):1441-7
references: 2864394