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Local Gabaergic Modulation of the Activity of Serotoninergic Neurons in the Nucleus Raphe Magnus

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Experiments on rat brainstem sections in membrane potential clamping conditions addressed the effects of serotonin and GABA on serotoninergic neurons in the nucleus raphe magnus. Local application of serotonin stimulated inhibitory postsynaptic currents (IPSC) in 45% of the serotoninergic neurons studied. This response was not seen in the presence of the fast sodium channel blocker tetrodotoxin. The GABAA receptor antagonist gabazine blocked IPSC in both serotonin-sensitive and serotonin-insensitive neurons. Application of GABA evoked generation of a membrane current (IGABA), which was completely blocked by gabazine. These results indicate self-regulation of the activity of serotoninergic neurons in the nucleus raphe magnus via a negative feedback circuit involving local GABAergic interneurons.

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References

  1. B. Yu. Mileikovskii and A. D. Nozdrachev, “Electrophysiological analysis of the interaction of the neuron population of the pons and the medulla oblongata involved in the inhibition of motor activity,” Ros. Fiziol. Zh. im. I. M. Sechenova, 83, No. 11–12, 57–63 (1997).

    Google Scholar 

  2. M. Alreja, “Excitatory actions of serotonin on GABAergic neurons of the medial septum and diagonal band of Broca,” Synapse, 22, 15–27 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. E. Bagdy, I. Kiraly, and L. G. Harsing, “Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat,” Neurochem. Res., 25, 1465–1473 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. N. G. Bowery, A. L. Hudson, and G. W. Price, “GABAA and GABAB receptors site distribution in the rat central nervous system,” Neuroscience, 20, 365–383 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. Y. Cao, K. Matsuyama, Y. Fujito, and M. Aoki, “Involvement of medullary GABAergic and serotonergic raphe neurons in respiratory control: Electrophysiological and immunohistochemical studies in rats,” Neurosci. Res., 56, 322–331 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. G. Chazal and H. J. Ralston II, “Serotonin-containing structures in the nucleus raphe dorsalis of the cat: an ultrastructural analysis of dendrites, presynaptic dendrites, and axon collaterals,” J. Comp. Neurol., 259, 259–317 (1987).

    Article  Google Scholar 

  7. H. J. Cho and A. I. Basbaum, “GABAergic circuitry in the rostral ventral medulla of the rat and its relationship to descending antinociceptive controls,” J. Comp. Neurol., 303, 316–328 (1991).

    Article  CAS  PubMed  Google Scholar 

  8. F. Crespi, J. C. Garratt, A. J. Sleight, and C. A. Marsden, “In vivo evidence that 5-hydroxytryptamine (5-HT) neuronal firing and release are not necessarily correlated with 5-HT metabolism,” Neuroscience, 35, 139–144 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. L. F. S. da Silva and L. Menescal-de-Oliveira, “Role of opioidergic and GABAergic neurotransmission of the nucleus raphe magnus in the modulation of tonic immobility in guinea pigs,” Brain Res. Bull., 72, 25–31 (2007).

    Article  PubMed  Google Scholar 

  10. C. Davidson and J. A. Stamford, “Evidence that 5-hydroxytryptamine release in rat dorsal raphe nucleus is controlled by 5-HT1A, 5-HT1B and 5-HT1D autoreceptors,” Brit. J. Pharmacol., 114, 1107–1109 (1995).

    CAS  Google Scholar 

  11. H. U. Dodt and W. Zieglgänsberger, “Visualizing unstained neurons in living brain slices by infrared DIC-videomicroscopy,” Brain Res., 537, 333–336 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. K. Gao and P. Mason, “Somatodendritic and axonal anatomy of intracellularly labeled serotonergic neurons in the rat medulla,” J. Comp. Neurol., 389, 309–328 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. D. Gervasconi, C. Peyron, C. Rampon, B. Barbagli, G. Chouvet, N. Urbain, P. Fort, and P. H. Luppi, “Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons,” J. Neurosci., 20, 4217–4225 (2000).

    Google Scholar 

  14. M. Hajos, S. E. Gartside, A. E. P. Villa, and T. Sharp, “Evidence for a repetitive (burst) firing pattern in a sub-population in the dorsal and median raphe nuclei of the rat,” Neuroscience, 69, 189–197 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. I. D. Hentall, P. J. Furle, and T. R. White, “Correlations between serotonin level and single-cell firing in the rat’s nucleus raphe magnus,” Neuroscience, 95, 1081–1088 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. F. Hery, M. Faudon, and J. P. Ternaux, “In vivo release of serotonin in two raphe nuclei (raphe dorsalis and magnus) of cat,” Brain Res. Bull., 8, 123–129 (1982).

    Article  CAS  PubMed  Google Scholar 

  17. J.-P. Hornung, “The human raphe nuclei and the serotonergic system,” J. Chem. Neuroanat., 26, 331–343 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. I. A. Kerman, C. Shabrang, L. Taylor, H. Akil, and S. J. Watson, “Relationship of presympathetic-premotor neurons to the serotonergic transmitter system in the brainstem,” J. Comp. Neurol., 499, 882–896 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Y. W. Li and D. A. Bayliss, “Electrophysical properties, synaptic transmission and neuromodulation in serotonergic caudal raphe neurons,” Clin. Exp. Pharmacol. Physiol., 25, 468–473 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. A. H. Li and H.-L. Wang, “G protein-coupled receptor kinase 2 mediated μ-opioid receptor desensitization in GABAergic neurons of the nucleus raphe magnus,” J. Neurochem., 77, 435–444 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. R. Liu, T. Jolas, and G. K. Aghajanian, “Serotonin 5-HT2 receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus,” Brain Res., 873, 34–45 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. P. Mason, “Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions,” Ann. Rev. Neurosci., 24, 737–777 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. P. Mason, “Deconstructing endogenous pain modulations,” J. Neurophysiol., 94, 1659–1663 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. P. Mason, K. Gao, and J. R. Gensen, “Serotonergic raphe magnus cell discharge reflects ongoing autonomic and respiratory activities,” J. Neurophysiol., 98, 1919–1927 (2007).

    Article  PubMed  Google Scholar 

  25. L. L. McMahon and J. A. Kauer, “Hippocampal interneurons are excited via serotonin-gated ion channels,” J. Neurophysiol., 78, 2493–2502 (1997).

    CAS  PubMed  Google Scholar 

  26. J. A. Mico, E. Berrocoso, A. Ortega-Alvaro, J. Gibert-Rahola, and M. O. Rojas-Corrales, “The role of 5-HT1A receptors in research strategy for extensive pain treatment,” Curr. Top. Med. Chem., 18, 1997–2003 (2006).

    Article  Google Scholar 

  27. D. E. Millhorn, T. Hokfelt, K. Seroogy, and A. A. Verhofstad, “Extent of colocalization of serotonin and GABA in neurons of the ventral medulla oblongata in rat,” Brain Res., 461, 169–174 (1988).

    Article  CAS  PubMed  Google Scholar 

  28. M. K. Mundey, A. Fletcher, and C. A. Marsden, “Effect of the putative 5-HT]A antagonists WAY 100135 and SDZ 216-525 on 5-HT neuronal firing in the guinea-pig dorsal raphe nucleus,” Neuropharmacol., 33, 61–66 (1994).

    Article  CAS  Google Scholar 

  29. K. T. Muneoka and M. Takigawa, “5-Hydroxytryptamine7 (5-HT7) receptor immunoreactivity-positive ‘stigmoid body’-like structure in developing rat brains,” Int. J. Dev. Neurosci., 21, 133–143 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. T. Nagai, T. Maeda, H. Imai, P. L. McGeer, and E. G. McGeer, “Distribution of GABA-T-intensive neurons in the rat hindbrain,” J. Comp. Neurol., 231, 260–269 (1985).

    Article  CAS  PubMed  Google Scholar 

  31. M. W. Nason and P. Mason, “Medullary raphe neurons facilitate brown adipose tissue activation,” J. Neurosci., 26, 1190–1198 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Z. Z. Pan, S. A. Tershner, and H. L. Fields, “Cellular mechanism for anti-analgesic action of agonists of the kappa-opioid receptor,” Nature, 389, 382–385 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. N. J. Penington, J. S. Kelly, and A. P. Fox, “Whole cell recordings of inwardly rectifying K+ currents activated by 5-HT1A receptors on dorsal raphe neurons of the adult rat,” J. Physiol., 469, 387–406 (1993).

    CAS  PubMed  Google Scholar 

  34. N. J. Penington and J. S. Kelly, “Serotonin receptor activation reduces calcium current in an acutely dissociated adult central neuron,” Neuron, 4, 751–758 (1990).

    Article  CAS  PubMed  Google Scholar 

  35. M. Pompeiano, J. M. Palacios, and G. Mengod, “Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding,” J. Neurosci., 12, 440–453 (1992).

    CAS  PubMed  Google Scholar 

  36. S. B. Potrebic, H. L. Fields, and P. Mason, “Serotonin immunoreactivity is contained in one physiological cell class in the rat rostral ventromedial medulla,” J. Neurosci., 14, 1655–1665 (1994).

    CAS  PubMed  Google Scholar 

  37. D. B. Reichling and A. I. Basbaum, “Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: II. Electronic microscopic immunocytochemical evidence, of GABAergic control over the projection from the periaqueductal gray to the nucleus raphe magnus in the rat,” J. Comp. Neurol., 302, 378–393 (1990).

    Article  CAS  PubMed  Google Scholar 

  38. W. M. Renno, M. Alkhalaf, A. Mousa, and R. A. Kanaan, “A comparative study of excitatory and inhibitory amino acids in three different brainstem nuclei,” Neurochem. Res., 33, 150–159 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. J. Serrats, F. Artigas, G. Mengod, and R. Cortes, “GABAB receptor mRNA in the raphe nuclei: co-expression with serotonin transporter and glutamic acid decarboxylase,” J. Neurochem., 84, 743–752 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. C. Sotelo, B. Cholley, S. E. Mestikawy, H. Gozlan, and M. Hamon, “Direct immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei,” Eur. J. Neurosci., 2, 144–154 (1990).

    Article  Google Scholar 

  41. L. M. Sharkey, S. G. Madamba, G. Siggins, and T. Bartfai, “Galanin alters GABAergic neurotransmission in the dorsal raphe nucleus,” Neurochem. Res., 33, 285–291 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. R. Tao, Z. Ma, and S. B. Auerbach, “Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats,” Brit. J. Pharmacol., 119, 1375–1384 (1996).

    CAS  Google Scholar 

  43. Y. Tohyama, D. Muck-Seler, and M. Diksic, “Acute flesinoxan treatment produces a different effect on rat brain serotonin synthesis than chronic treatment: An α-methyl-L-tryptophan autoradiographic study,” Neurochem. Int., 51, 486–495 (2007).

    Article  CAS  PubMed  Google Scholar 

  44. N. Urbain, K. Creamer, and G. Debonnel, “Electrophysiological diversity of the dorsal raphe cells across the sleep-wake cycle of the rat,” J. Physiol., 573, 679–695 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. C. P. Candermaelen and G. K. Aghajanian, “Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices,” Brain Res., 289, 109–119 (1983).

    Article  Google Scholar 

  46. T. A. Verner, A. K. Goodchild, and P. M. Pokowsky, “A mapping study of cardiorespiratory responses to chemical stimulation of the midline medulla oblongata in ventilated and freely breathing rats,” Am. J. Physiol., 287, R411–R421 (2004).

    Article  CAS  Google Scholar 

  47. D. M. L. Vianna, C. Allen, and P. Carrive, “Cardiovascular and behavioral responses to conditioned fear after medullary raphe neuronal blockade,” Neuroscience, 153, 1344–1353 (2008).

    Article  CAS  PubMed  Google Scholar 

  48. L. Zhang, K. T. Sykes, A. V. Vuhler, and D. L. Hammond, “Electrophysiological heterogeneity of spinally projecting serotonergic and nonserotonergic neurons in the rostral ventromedial medulla,” J. Neurophysiol., 95, 1853–1863 (2006).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Samara State University, 1 Academician Pavlov Street, 443016, Samara, Russia

    A. N. Inyushkin, N. A. Merkulova, A. O. Orlova & E. M. Inyushkina

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  1. A. N. Inyushkin
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  2. N. A. Merkulova
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  3. A. O. Orlova
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Correspondence to A. N. Inyushkin.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 95, No. 7, pp. 750–761, July, 2009.

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Inyushkin, A.N., Merkulova, N.A., Orlova, A.O. et al. Local Gabaergic Modulation of the Activity of Serotoninergic Neurons in the Nucleus Raphe Magnus. Neurosci Behav Physi 40, 885–893 (2010). https://doi.org/10.1007/s11055-010-9337-x

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