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GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity

Nature volume 387, pages 598–603 (1997)Cite this article

Abstract

Mammals manifest circadian behaviour timed by an endogenous clock in the hypothalamic suprachiasmatic nucleus (SCN)1. Considerable progress has been made in identifying the molecular basis of the circadian clock2,3, but the mechanisms by which it is translated into cyclic firing activity, high during the day and low at night, are still poorly understood. GABA (γ-aminobutyric acid), a common inhibitory neurotransmitter in the central nervous system, is particularly densely distributed within the SCN, where it is located in the majority of neuronal somata4,5 and synaptic terminals6,7. Using an in vitro brain-slice technique, we have now studied the effect of bath-applied GABA on adult SCN neurons at various times of the day. We find that GABA acts as an inhibitory neurotransmitter at night, decreasing the firing frequency; but during the day GABA acts as an excitatory neurotransmitter, increasing the firing frequency. We show that this dual effect, which is mediated by GABAA receptors, may be attributed to an oscillation in intracellular chloride concentration. A likely explanation is that the amplitude of the oscillation in firing rate, displayed by individual neurons, is amplified by the dual effect of GABA in the SCN's GABAergic network.

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Figure 1: Immunocytochemical evidence for the extensive GABAergic innervation in the rat SCN.
Figure 2: GABA acts as an excitatory neurotransmitter during the day and as an inhibitory neurotransmitter at night.
Figure 3: Neither the conductance change nor the reversal potential of the GABA response depend on the time of the day when the whole-cell patch technique was used.
Figure 4: Most of the spontaneous synaptic potentials are GABAergic, and may be used to estimate the intracellular chloride concentration.
Figure 5: Postulated diurnal alterations in [Cl−]i revealed by analysing the amplitude of the spontaneous synaptic potentials.

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Acknowledgements

We thank M. Belenky for perfecting the organotypic slice explant culture technique; H. Matzner and S. Cohen for technical assistance; and J. Morris for critical reading of the text. Research was supported by the USA–Israel Binational Science Foundation and the Israel Ministry of Science and Technology.

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Authors and Affiliations

  1. Departments of Neurobiology, Institute of Life Sciences, Hebrew University, 91904, Jerusalem, Israel

    Shlomo Wagner & Yosef Yarom

  2. *Cell and Animal Biology, Institute of Life Sciences, Hebrew University, 91904, Jerusalem, Israel

    Mona Castel

  3. †Laboratory of Neurochemistry, National Institutes of Health, NINDS, Bethesda, 20892, Maryland, USA

    Harold Gainer

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  1. Shlomo Wagner
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  2. Mona Castel
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  4. Yosef Yarom
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Correspondence to Shlomo Wagner.

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Wagner, S., Castel, M., Gainer, H. et al. GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity. Nature 387, 598–603 (1997). https://doi.org/10.1038/42468

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