Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1992 Dec;458:247–260. doi: 10.1113/jphysiol.1992.sp019416

Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: inhibitory synaptic mechanisms.

Y I Kim 1, F E Dudek 1
PMCID: PMC1175154  PMID: 1302267

Abstract

1. The mechanisms responsible for evoked and spontaneous fast inhibitory postsynaptic potentials (IPSPs) in the hypothalamic suprachiasmatic nucleus (SCN) were studied with intracellular recording. SCN neurons, primarily ones identified as receiving excitatory optic nerve input, were recorded in rat and guinea-pig brain slice preparations maintained in vitro. 2. In normal medium, electrical stimulation of a site dorsocaudal to the SCN evoked IPSPs from thirty-three of thirty-six neurons. The evoked IPSPs rose to the peak quickly (8.7 +/- 0.9 ms, mean +/- S.E.M.; n = 15 neurons) and decayed gradually with a time constant of 25 +/- 3 ms. Spontaneous IPSPs were present in each of the thirty-six neurons. These IPSPs had a rise-to-peak time of 7.2 +/- 1.0 ms (n = 6 neurons) and a decay time constant of 14 +/- 5 ms. 3. When recorded with potassium acetate-filled electrodes, the evoked and spontaneous IPSPs were hyperpolarizing at resting membrane potential (less negative than -70 mV) and had a reversal potential of around -75 mV. On the other hand, when recorded with potassium chloride-filled electrodes, the IPSPs were depolarizing at membrane potentials more negative than -50 mV and had an estimated reversal potential less negative than spike threshold. 4. Bath application of bicuculline (10-50 microM), a gamma-aminobutyric acidA (GABAA) receptor antagonist, resulted in a complete blockade of both the evoked (n = 16) and spontaneous (n = 13) IPSPs. The bicuculline effects were reversible, and were not associated with any significant and consistent change in baseline membrane potential or input resistance. The neurons impaled in bicuculline-containing medium (n = 11) exhibited neither spontaneous IPSPs nor evoked IPSPs. 5. In some neurons bicuculline-resistant hyperpolarizing potentials, which were similar to the fast IPSPs in time course, occurred spontaneously or were evoked by electrical stimulation of the optic nerve or the dorsocaudal site. A fast prepotential always preceded the hyperpolarizing potential, and hyperpolarizing currents blocked these events, indicating that they were not synaptic in origin. No slow IPSPs were detected. 6. The results suggest that fast IPSPs from non-retinal afferents exist in virtually all SCN neurons receiving excitatory retinal input, and that GABAA receptors associated with Cl- channels mediate the fast IPSPs.

Full text

PDF
247

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bosler O. Ultrastructural relationships of serotonin and GABA terminals in the rat suprachiasmatic nucleus. Evidence for a close interconnection between the two afferent systems. J Neurocytol. 1989 Feb;18(1):105–113. doi: 10.1007/BF01188429. [DOI] [PubMed] [Google Scholar]
  2. Card J. P., Moore R. Y. The suprachiasmatic nucleus of the golden hamster: immunohistochemical analysis of cell and fiber distribution. Neuroscience. 1984 Oct;13(2):415–431. doi: 10.1016/0306-4522(84)90240-9. [DOI] [PubMed] [Google Scholar]
  3. Christian E. P., Dudek F. E. Electrophysiological evidence from glutamate microapplications for local excitatory circuits in the CA1 area of rat hippocampal slices. J Neurophysiol. 1988 Jan;59(1):110–123. doi: 10.1152/jn.1988.59.1.110. [DOI] [PubMed] [Google Scholar]
  4. Decavel C., Van den Pol A. N. GABA: a dominant neurotransmitter in the hypothalamus. J Comp Neurol. 1990 Dec 22;302(4):1019–1037. doi: 10.1002/cne.903020423. [DOI] [PubMed] [Google Scholar]
  5. Dutar P., Nicoll R. A. A physiological role for GABAB receptors in the central nervous system. Nature. 1988 Mar 10;332(6160):156–158. doi: 10.1038/332156a0. [DOI] [PubMed] [Google Scholar]
  6. Hasuo H., Gallagher J. P. Comparison of antagonism by phaclofen of baclofen induced hyperpolarizations and synaptically mediated late hyperpolarizing potentials recorded intracellularly from rat dorsolateral septal neurons. Neurosci Lett. 1988 Mar 21;86(1):77–81. doi: 10.1016/0304-3940(88)90186-3. [DOI] [PubMed] [Google Scholar]
  7. Johnson R. F., Smale L., Moore R. Y., Morin L. P. Lateral geniculate lesions block circadian phase-shift responses to a benzodiazepine. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5301–5304. doi: 10.1073/pnas.85.14.5301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Karlsson G., Olpe H. R. Late inhibitory postsynaptic potentials in rat prefrontal cortex may be mediated by GABAB receptors. Experientia. 1989 Feb 15;45(2):157–158. doi: 10.1007/BF01954857. [DOI] [PubMed] [Google Scholar]
  9. Kim Y. I., Dudek F. E. Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: excitatory synaptic mechanisms. J Physiol. 1991 Dec;444:269–287. doi: 10.1113/jphysiol.1991.sp018877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liou S. Y., Albers H. E. Single unit response of neurons within the hamster suprachiasmatic nucleus to GABA and low chloride perfusate during the day and night. Brain Res Bull. 1990 Jul;25(1):93–98. doi: 10.1016/0361-9230(90)90257-z. [DOI] [PubMed] [Google Scholar]
  11. Liou S. Y., Shibata S., Albers H. E., Ueki S. Effects of GABA and anxiolytics on the single unit discharge of suprachiasmatic neurons in rat hypothalamic slices. Brain Res Bull. 1990 Jul;25(1):103–107. doi: 10.1016/0361-9230(90)90259-3. [DOI] [PubMed] [Google Scholar]
  12. Mason R., Biello S. M., Harrington M. E. The effects of GABA and benzodiazepines on neurones in the suprachiasmatic nucleus (SCN) of Syrian hamsters. Brain Res. 1991 Jun 21;552(1):53–57. doi: 10.1016/0006-8993(91)90659-j. [DOI] [PubMed] [Google Scholar]
  13. McCormick D. A. GABA as an inhibitory neurotransmitter in human cerebral cortex. J Neurophysiol. 1989 Nov;62(5):1018–1027. doi: 10.1152/jn.1989.62.5.1018. [DOI] [PubMed] [Google Scholar]
  14. Meijer J. H., Rietveld W. J. Neurophysiology of the suprachiasmatic circadian pacemaker in rodents. Physiol Rev. 1989 Jul;69(3):671–707. doi: 10.1152/physrev.1989.69.3.671. [DOI] [PubMed] [Google Scholar]
  15. Moore R. Y. Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc. 1983 Aug;42(11):2783–2789. [PubMed] [Google Scholar]
  16. Okamura H., Bérod A., Julien J. F., Geffard M., Kitahama K., Mallet J., Bobillier P. Demonstration of GABAergic cell bodies in the suprachiasmatic nucleus: in situ hybridization of glutamic acid decarboxylase (GAD) mRNA and immunocytochemistry of GAD and GABA. Neurosci Lett. 1989 Jul 31;102(2-3):131–136. doi: 10.1016/0304-3940(89)90067-0. [DOI] [PubMed] [Google Scholar]
  17. Rall W. Time constants and electrotonic length of membrane cylinders and neurons. Biophys J. 1969 Dec;9(12):1483–1508. doi: 10.1016/S0006-3495(69)86467-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ralph M. R., Menaker M. Bicuculline blocks circadian phase delays but not advances. Brain Res. 1985 Jan 28;325(1-2):362–365. doi: 10.1016/0006-8993(85)90341-5. [DOI] [PubMed] [Google Scholar]
  19. Ralph M. R., Menaker M. Effects of diazepam on circadian phase advances and delays. Brain Res. 1986 May 7;372(2):405–408. doi: 10.1016/0006-8993(86)91154-6. [DOI] [PubMed] [Google Scholar]
  20. Ralph M. R., Menaker M. GABA regulation of circadian responses to light. I. Involvement of GABAA-benzodiazepine and GABAB receptors. J Neurosci. 1989 Aug;9(8):2858–2865. doi: 10.1523/JNEUROSCI.09-08-02858.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Randle J. C., Bourque C. W., Renaud L. P. Characterization of spontaneous and evoked inhibitory postsynaptic potentials in rat supraoptic neurosecretory neurons in vitro. J Neurophysiol. 1986 Dec;56(6):1703–1717. doi: 10.1152/jn.1986.56.6.1703. [DOI] [PubMed] [Google Scholar]
  22. Shibata S., Liou S. Y., Ueki S. Different effects of amino acids, acetylcholine and monoamines on neuronal activity of suprachiasmatic nucleus in rat pups and adults. Neurosci Lett. 1983 Aug 29;39(2):187–192. doi: 10.1016/0304-3940(83)90075-7. [DOI] [PubMed] [Google Scholar]
  23. Smith R. D., Inouye S., Turek F. W. Central administration of muscimol phase-shifts the mammalian circadian clock. J Comp Physiol A. 1989 Feb;164(6):805–814. doi: 10.1007/BF00616752. [DOI] [PubMed] [Google Scholar]
  24. Soltesz I., Haby M., Leresche N., Crunelli V. The GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurones. Brain Res. 1988 May 17;448(2):351–354. doi: 10.1016/0006-8993(88)91275-9. [DOI] [PubMed] [Google Scholar]
  25. Soltesz I., Lightowler S., Leresche N., Crunelli V. Optic tract stimulation evokes GABAA but not GABAB IPSPs in the rat ventral lateral geniculate nucleus. Brain Res. 1989 Feb 6;479(1):49–55. doi: 10.1016/0006-8993(89)91334-6. [DOI] [PubMed] [Google Scholar]
  26. Takahashi J. S., Zatz M. Regulation of circadian rhythmicity. Science. 1982 Sep 17;217(4565):1104–1111. doi: 10.1126/science.6287576. [DOI] [PubMed] [Google Scholar]
  27. Tappaz M. L., Brownstein M. J., Kopin I. J. Glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in discrete nuclei of hypothalamus and substantia nigra. Brain Res. 1977 Apr 8;125(1):109–121. doi: 10.1016/0006-8993(77)90363-8. [DOI] [PubMed] [Google Scholar]
  28. Thomson A. M., West D. C. Factors affecting slow regular firing in the suprachiasmatic nucleus in vitro. J Biol Rhythms. 1990 Spring;5(1):59–75. doi: 10.1177/074873049000500106. [DOI] [PubMed] [Google Scholar]
  29. Turek F. W. Circadian neural rhythms in mammals. Annu Rev Physiol. 1985;47:49–64. doi: 10.1146/annurev.ph.47.030185.000405. [DOI] [PubMed] [Google Scholar]
  30. Turek F. W., Van Reeth O. Altering the mammalian circadian clock with the short-acting benzodiazepine, triazolam. Trends Neurosci. 1988 Dec;11(12):535–541. doi: 10.1016/0166-2236(88)90181-6. [DOI] [PubMed] [Google Scholar]
  31. Wheal H. V., Thomson A. M. The electrical properties of neurones of the rat suprachiasmatic nucleus recorded intracellularly in vitro. Neuroscience. 1984 Sep;13(1):97–104. doi: 10.1016/0306-4522(84)90262-8. [DOI] [PubMed] [Google Scholar]
  32. van den Pol A. N. Gamma-aminobutyrate, gastrin releasing peptide, serotonin, somatostatin, and vasopressin: ultrastructural immunocytochemical localization in presynaptic axons in the suprachiasmatic nucleus. Neuroscience. 1986 Mar;17(3):643–659. doi: 10.1016/0306-4522(86)90037-0. [DOI] [PubMed] [Google Scholar]
  33. van den Pol A. N., Tsujimoto K. L. Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. Neuroscience. 1985 Aug;15(4):1049–1086. doi: 10.1016/0306-4522(85)90254-4. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES