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PMID: 12042351 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Serotonin suppresses the slow afterhyperpolarization in rat intralaminar and midline thalamic neurones by activating 5-HT(7) receptors.

The Journal of physiology ·Vol. 541 ·No. Pt 2 ·2002-06-01 ·Pages 453-65

Goaillard JM, Vincent P

Abstract

While the highest expression level of 5-HT(7) receptors in the brain is observed in intralaminar and midline thalamic neurones, the physiological role of these receptors in this structure is unknown. In vivo recordings have shown that stimulation of the serotonergic raphe nuclei can alter the response of these neurones to a nociceptive stimulus, suggesting that serotonin modulates their firing properties. Using the patch-clamp technique in rat thalamic brain slices, we demonstrate that activation of 5-HT(7) receptors can strongly modulate the excitability of intralaminar and midline thalamic neurones by inhibiting the calcium-activated potassium conductance that is responsible for the slow afterhyperpolarization (sAHP) following a spike discharge. This sAHP was inhibited after activation of the cAMP pathway, either by bath application of forskolin or intracellular perfusion with 8-bromo-cAMP. The inhibitory effect of 5-HT(7) receptors on sAHPs was blocked by the protein kinase A antagonist R(P)-cAMPS. Calcium-imaging experiments showed no change in intracellular calcium levels during the 5-HT(7) response, indicating that in these neurones, a global calcium signal was not necessary to activate the cAMP cascade. Finally, bath application of serotonin produced a strong increase in cytosolic cAMP concentration, as measured using the fluorescent probe FlCRhR, and an inhibition of the sAHP. Taken together, these results suggest that 5-HT(7) receptors are implicated in the effect of 5-HT on sAHP in intralaminar and midline thalamic neurones, an effect that is mediated by the cAMP second-messenger cascade.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Animals Calcium Signaling/drug effects Colforsin/pharmacology Cyclic AMP/physiology Cyclic AMP-Dependent Protein Kinases/metabolism Electrophysiology Fluorescent Dyes In Vitro Techniques Kinetics Membrane Potentials/drug effects,physiology Neurons/drug effects Patch-Clamp Techniques Rats Receptors, Serotonin/drug effects Serotonin/pharmacology Serotonin Receptor Agonists/pharmacology Thalamus/cytology,drug effects
Chemicals
Fluorescent Dyes Receptors, Serotonin Serotonin Receptor Agonists serotonin 7 receptor Colforsin 8-Bromo Cyclic Adenosine Monophosphate Serotonin Cyclic AMP Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Goaillard Jean-Marc
Equipe Neurobiologie Cellulaire, Neurobiologie des Processus Adaptatifs UMR 7102, CNRS Université Paris VI, F-75005 Paris, France.
Vincent Pierre
References (51)
51 references, click to expand
  1. Type VIII adenylyl cyclase. A Ca2+/calmodulin-stimulated enzyme expressed in discrete regions of rat brain.
    J Biol Chem. 1994 Apr 22;269(16):12190-5 PMID: 8163524
  2. Apamin, a neurotoxin specific for one class of Ca2+-dependent K+ channels.
    Cell Calcium. 1983 Dec;4(5-6):421-8 PMID: 6323004
  3. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain.
    Br J Pharmacol. 1996 Feb;117(4):657-66 PMID: 8646411
  4. Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
    Trends Neurosci. 1996 Apr;19(4):150-4 PMID: 8658599
  5. Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states.
    Drugs Aging. 1996 Jun;8(6):459-76 PMID: 8736630
  6. Differential expression of type I, II, and V adenylyl cyclase gene in the postnatal developing rat brain.
    J Neurochem. 1997 Feb;68(2):498-506 PMID: 9003034
  7. Expression of 5-HT7 receptor mRNA in rat brain during postnatal development.
    Neurosci Lett. 1997 May 9;227(1):53-6 PMID: 9178857
  8. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b).
    Br J Pharmacol. 1997 Sep;122(1):126-32 PMID: 9298538
  9. Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons.
    J Neurophysiol. 1998 Jun;79(6):2911-8 PMID: 9636097
  10. Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by the Gs-coupled 5-hydroxytryptamine subtype 5-HT7A receptor.
    J Biol Chem. 1998 Jul 10;273(28):17469-76 PMID: 9651336
  11. Calcium-activated potassium channels.
    Curr Opin Neurobiol. 1998 Jun;8(3):321-9 PMID: 9687354
  12. Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.
    Br J Pharmacol. 1998 Jul;124(6):1300-6 PMID: 9720804
  13. Functional characterization of the recombinant human 5-hydroxytryptamine7(a) receptor isoform coupled to adenylate cyclase stimulation.
    J Pharmacol Exp Ther. 1998 Nov;287(2):508-14 PMID: 9808674
  14. Function and distribution of three rat 5-hydroxytryptamine7 (5-HT7) receptor isoforms produced by alternative splicing.
    Neuropharmacology. 1998 Dec;37(12):1621-32 PMID: 9886685
  15. Tetrahydrobenzindoles: selective antagonists of the 5-HT7 receptor.
    J Med Chem. 1999 Feb 25;42(4):533-5 PMID: 10052959
  16. Projections of the median raphe nucleus in the rat.
    J Comp Neurol. 1999 May 17;407(4):555-82 PMID: 10235645
  17. Photolytic manipulation of [Ca2+]i reveals slow kinetics of potassium channels underlying the afterhyperpolarization in hippocampal pyramidal neurons.
    J Neurosci. 1999 May 15;19(10):3657-64 PMID: 10233997
  18. A review of central 5-HT receptors and their function.
    Neuropharmacology. 1999 Aug;38(8):1083-152 PMID: 10462127
  19. Psychological and neural mechanisms of the affective dimension of pain.
    Science. 2000 Jun 9;288(5472):1769-72 PMID: 10846154
  20. 5-Hydroxytryptamine(7) receptor activation decreases slow afterhyperpolarization amplitude in CA3 hippocampal pyramidal cells.
    J Pharmacol Exp Ther. 2000 Aug;294(2):672-9 PMID: 10900247
  21. Simultaneous measurements of intracellular cAMP and L-type Ca2+ current in single frog ventricular myocytes.
    J Physiol. 2001 Jan 1;530(Pt 1):79-91 PMID: 11136860
  22. Potassium leak channels and the KCNK family of two-P-domain subunits.
    Nat Rev Neurosci. 2001 Mar;2(3):175-84 PMID: 11256078
  23. A 5-HT(7) receptor-mediated depolarization in the anterodorsal thalamus. II. Involvement of the hyperpolarization-activated current I(h).
    J Pharmacol Exp Ther. 2001 Apr;297(1):403-9 PMID: 11259569
  24. Cyclic AMP imaging in neurones in brain slice preparations.
    J Neurosci Methods. 2001 Jul 30;108(2):189-98 PMID: 11478978
  25. Novel action of BAPTA series chelators on intrinsic K+ currents in rat hippocampal neurones.
    J Physiol. 2000 Jan 15;522 Pt 2:231-46 PMID: 10639100
  26. 5-HT7 receptors: current knowledge and future prospects.
    Trends Pharmacol Sci. 2000 Feb;21(2):70-7 PMID: 10664612
  27. A novel, potent, and selective 5-HT(7) antagonist: (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl) phen ol (SB-269970).
    J Med Chem. 2000 Feb 10;43(3):342-5 PMID: 10669560
  28. Protein kinase A mediates the modulation of the slow Ca(2+)-dependent K(+) current, I(sAHP), by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons.
    J Neurophysiol. 2000 Apr;83(4):2071-9 PMID: 10758117
  29. Diencephalic connections of the raphé nuclei of the rat brainstem: an anatomical study with reference to the somatosensory system.
    J Comp Neurol. 1984 Apr 20;224(4):509-34 PMID: 6725629
  30. Diencephalic mechanisms of pain sensation.
    Brain Res. 1985 Aug;356(3):217-96 PMID: 3896408
  31. Noradrenergic modulation of firing pattern in guinea pig and cat thalamic neurons, in vitro.
    J Neurophysiol. 1988 Mar;59(3):978-96 PMID: 3367206
  32. The coupling of neurotransmitter receptors to ion channels in the brain.
    Science. 1988 Jul 29;241(4865):545-51 PMID: 2456612
  33. Dorsal raphe stimulation modulates nociceptive responses in thalamic parafascicular neurons via an ascending pathway: further studies on ascending pain modulation pathways.
    Pain. 1988 Jul;34(1):65-74 PMID: 3405622
  34. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system.
    Pflugers Arch. 1989 Sep;414(5):600-12 PMID: 2780225
  35. Intrinsic properties of nucleus reticularis thalami neurones of the rat studied in vitro.
    J Physiol. 1989 Sep;416:111-22 PMID: 2558172
  36. Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex.
    J Neurosci Methods. 1989 Dec;30(3):203-10 PMID: 2607782
  37. A controlled study of psychotherapy and amitriptyline used individually and in combination in the treatment of chronic intractable, 'psychogenic' pain.
    Pain. 1990 Jan;40(1):3-19 PMID: 2339013
  38. Nociceptive responses in medial thalamus of the normal and arthritic rat.
    Pain. 1990 Jan;40(1):93-104 PMID: 2339022
  39. High affinity forskolin inhibition of L-type Ca2+ current in cardiac cells.
    Mol Pharmacol. 1990 Dec;38(6):758-65 PMID: 1701212
  40. Fluorescence ratio imaging of cyclic AMP in single cells.
    Nature. 1991 Feb 21;349(6311):694-7 PMID: 1847505
  41. GABAA receptor phosphorylation: multiple sites, actions and artifacts.
    Trends Pharmacol Sci. 1991 Mar;12(3):84-7 PMID: 1647063
  42. Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones.
    J Physiol. 1990 Dec;431:319-42 PMID: 1712844
  43. Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal.
    J Neurosci. 1991 Oct;11(10):3188-99 PMID: 1658246
  44. Long-term increases in excitability in the CA1 region of rat hippocampus induced by beta-adrenergic stimulation: possible mediation by cAMP.
    J Neurosci. 1992 Feb;12(2):506-17 PMID: 1311033
  45. Adenosine promotes burst activity in guinea-pig geniculocortical neurones through two different ionic mechanisms.
    J Physiol. 1992 Feb;447:729-53 PMID: 1593463
  46. Vasoactive intestinal polypeptide modulates neuronal excitability in hippocampal slices of the rat.
    Neuroscience. 1992;47(2):273-7 PMID: 1322509
  47. Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.
    J Biol Chem. 1993 Aug 25;268(24):18200-4 PMID: 8394362
  48. Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in vitro: a mammalian pacemaker.
    J Physiol. 1993 Aug;468:669-91 PMID: 8254530
  49. PKA mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons.
    Neuron. 1993 Dec;11(6):1023-35 PMID: 8274274
  50. Dorsal raphe stimulation reduces responses of parafascicular neurons to noxious stimulation.
    Pain. 1983 Apr;15(4):323-31 PMID: 6306539
  51. Chronic morphine administration causes region-specific increase of brain type VIII adenylyl cyclase mRNA.
    Eur J Pharmacol. 1994 Jul 15;268(2):215-21 PMID: 7957643
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2001.013896
Published
2002-06-01
Pages
453-65
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2290335
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.2001.013896 PMC Full Text View journal details
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