title: Excitatory effects of thyrotropin-releasing hormone in the thalamus.
abstract: The activity of the thalamus is state dependent. During slow-wave sleep, rhythmic burst firing is prominent, whereas during waking or rapid eye movement sleep, tonic, single-spike activity dominates. These state-dependent changes result from the actions of modulatory neurotransmitters. In the present study, we investigated the functional and cellular effects of the neuropeptide thyrotropin-releasing hormone (TRH) on the spontaneously active ferret geniculate slice. This peptide and its receptors are prominently expressed in the thalamic network, yet the role of thalamic TRH remains obscure. Bath application of TRH resulted in a transient cessation of both spindle waves and the epileptiform slow oscillation induced by application of bicuculline. With intracellular recordings, TRH application to the GABAergic neurons of the perigeniculate (PGN) or thalamocortical cells in the lateral geniculate nucleus resulted in depolarization and increased membrane resistance. In perigeniculate neurons, this effect reversed near the reversal potential for K+, suggesting that it is mediated by a decrease in K+ conductance. In thalamocortical cells, the TRH-induced depolarization was of sufficient amplitude to block the generation of rebound Ca2+ spikes, whereas the even larger direct depolarization of PGN neurons transformed these cells from the burst to tonic, single-spike mode of action potential generation. Furthermore, application of TRH prominently enhanced the afterdepolarization that follows rebound Ca2+ spikes, suggesting that this transmitter may also enhance Ca2+-activated nonspecific currents. These data suggest a novel role for TRH in the brain as an intrinsic regulator of thalamocortical network activity and provide a potential mechanism for the wake-promoting and anti-epileptic effects of this peptide.
authors.affiliation: Kavli Institute for Neuroscience and Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Broberger
authors.forename: David A
authors.initials: DA
authors.lastname: McCormick
mesh_terms: D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D005289:Ferrets; D018756:GABA Antagonists / Q000494:pharmacology; D005829:Geniculate Bodies / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D018721:Muscarinic Agonists; D015221:Potassium Channels; D011963:Receptors, GABA-A; D016210:Methacholine Chloride; D005680:gamma-Aminobutyric Acid; D013973:Thyrotropin-Releasing Hormone; D011188:Potassium; D001640:Bicuculline
references.citation: Neuroscience. 1999;91(4):1445-60
references.pmid: 10391450
references.citation: J Physiol. 1999 Dec 15;521 Pt 3:617-27
references.pmid: 10601493
references.citation: J Chem Neuroanat. 1999 Nov;17(3):147-52
references.pmid: 10609863
references.citation: Mol Endocrinol. 2000 Jan;14(1):183-93
references.pmid: 10628757
references.citation: Neuron. 2000 Feb;25(2):399-410
references.pmid: 10719894
references.citation: Br J Pharmacol. 2000 May;130(2):315-20
references.pmid: 10807668
references.citation: Neuroscience. 2000;98(3):513-22
references.pmid: 10869845
references.citation: J Comp Neurol. 2000 Dec 11;428(2):319-36
references.pmid: 11064370
references.citation: J Physiol. 2001 Feb 15;531(Pt 1):67-79
references.pmid: 11179392
references.citation: J Physiol. 2001 Feb 15;531(Pt 1):81-94
references.pmid: 11179393
references.citation: Annu Rev Physiol. 2001;63:815-46
references.pmid: 11181977
references.citation: Brain Dev. 2001 Nov;23(7):662-7
references.pmid: 11701274
references.citation: J Neurosci. 2002 Feb 1;22(3):718-27
references.pmid: 11826101
references.citation: Neuron. 2002 Mar 14;33(6):947-58
references.pmid: 11906700
references.citation: Brain Res. 2002 May 10;935(1-2):59-64
references.pmid: 12062473
references.citation: J Neurosci. 2002 Jul 1;22(13):5374-86
references.pmid: 12097489
references.citation: J Neurosci. 2003 Apr 1;23(7):2751-8
references.pmid: 12684461
references.citation: J Neurophysiol. 2003 Aug;90(2):1224-34
references.pmid: 12711712
references.citation: Prog Neurobiol. 1992 Oct;39(4):337-88
references.pmid: 1354387
references.citation: Brain Res. 1991 Apr 5;545(1-2):1-7
references.pmid: 1650272
references.citation: J Physiol. 1991 Oct;442:235-55
references.pmid: 1665858
references.citation: J Physiol. 1991 Nov;443:25-44
references.pmid: 1668337
references.citation: J Comp Neurol. 1991 Aug 15;310(3):316-36
references.pmid: 1723987
references.citation: J Neurophysiol. 1991 Jun;65(6):1528-41
references.pmid: 1875260
references.citation: Eur J Pharmacol. 1991 Apr 10;196(1):15-9
references.pmid: 1908388
references.citation: J Neurophysiol. 1990 Dec;64(6):1838-46
references.pmid: 2074467
references.citation: Nature. 1986 Jan 30-Feb 5;319(6052):402-5
references.pmid: 2418361
references.citation: Synapse. 1989;3(4):331-8
references.pmid: 2740992
references.citation: Epilepsia. 1987 Jan-Feb;28(1):49-55
references.pmid: 3024959
references.citation: Science. 1986 Jan 10;231(4734):159-61
references.pmid: 3079917
references.citation: Endocrinology. 1987 Jul;121(1):98-107
references.pmid: 3109882
references.citation: Nature. 1988 Jul 21;334(6179):246-8
references.pmid: 3398922
references.citation: J Physiol. 1986 Oct;379:429-49
references.pmid: 3560000
references.citation: J Neurosci. 1986 Jan;6(1):68-81
references.pmid: 3944624
references.citation: Biochem Biophys Res Commun. 1969 Nov 6;37(4):705-10
references.pmid: 4982117
references.citation: C R Acad Sci Hebd Seances Acad Sci D. 1969 Nov 12;269(19):1870-3
references.pmid: 4983502
references.citation: Arch Ital Biol. 1984 Mar;122(1):73-82
references.pmid: 6087765
references.citation: Proc Natl Acad Sci U S A. 1980 Mar;77(3):1651-5
references.pmid: 6103537
references.citation: J Physiol. 1982 Jun;327:219-46
references.pmid: 6181250
references.citation: J Comp Neurol. 1982 Oct 1;210(4):317-34
references.pmid: 6183297
references.citation: J Neurophysiol. 1983 Oct;50(4):798-818
references.pmid: 6631464
references.citation: J Neurophysiol. 1984 Jun;51(6):1196-219
references.pmid: 6737028
references.citation: J Physiol. 1984 Apr;349:205-26
references.pmid: 6737292
references.citation: Exp Neurol. 1981 Jul;73(1):55-77
references.pmid: 7250289
references.citation: Brain Res. 1980 Nov 3;200(2):341-54
references.pmid: 7417821
references.citation: J Neurophysiol. 1995 Sep;74(3):990-1000
references.pmid: 7500167
references.citation: J Physiol. 1995 Mar 15;483 ( Pt 3):641-63
references.pmid: 7776249
references.citation: J Physiol. 1995 Mar 15;483 ( Pt 3):665-85
references.pmid: 7776250
references.citation: Brain Res Brain Res Rev. 1994 Aug;19(3):319-25
references.pmid: 7820135
references.citation: Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):512-6
references.pmid: 7831321
references.citation: J Neurophysiol. 1994 Jun;71(6):2576-81
references.pmid: 7931539
references.citation: Psychopharmacol Commun. 1975;1(3):305-17
references.pmid: 817374
references.citation: Science. 1993 Oct 29;262(5134):679-85
references.pmid: 8235588
references.citation: J Physiol. 1993 Aug;468:669-91
references.pmid: 8254530
references.citation: J Biol Chem. 1993 Feb 5;268(4):2389-92
references.pmid: 8381407
references.citation: Science. 1993 Jul 16;261(5119):361-4
references.pmid: 8392750
references.citation: Neuroscience. 1995 Oct;68(4):1105-25
references.pmid: 8544986
references.citation: Epilepsia. 1996 Apr;37(4):328-31
references.pmid: 8603636
references.citation: Neuron. 1996 Aug;17(2):297-308
references.pmid: 8780653
references.citation: J Neurosci. 1996 Oct 1;16(19):5923-41
references.pmid: 8815875
references.citation: J Neurosci. 1997 Jan 1;17(1):70-82
references.pmid: 8987737
references.citation: Annu Rev Neurosci. 1997;20:185-215
references.pmid: 9056712
references.citation: J Neurophysiol. 1997 Apr;77(4):1829-43
references.pmid: 9114239
references.citation: J Neurosci. 1997 Aug 15;17(16):6401-8
references.pmid: 9236248
references.citation: J Neurophysiol. 1997 Sep;78(3):1726-9
references.pmid: 9310457
references.citation: J Neurosci. 1997 Nov 15;17(22):8894-908
references.pmid: 9348356
references.citation: Neuroscience. 1997 Mar;77(2):335-50
references.pmid: 9472394
references.citation: J Neurophysiol. 1998 Jun;79(6):2911-8
references.pmid: 9636097
references.citation: J Neurophysiol. 1998 Sep;80(3):1439-55
references.pmid: 9744951
references.citation: J Biol Chem. 1998 Nov 27;273(48):32281-7
references.pmid: 9822707
references.citation: Science. 1999 Jan 22;283(5401):541-3
references.pmid: 9915702