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The Intrinsic Optical Signal Evoked by Chiasm Stimulation in the Rat Suprachiasmatic Nuclei Exhibits GABAergic Day-Night Variation
Lorenz Trachsel,
Hans-Ulrich Dodt,
Walter Zieglgänsberger,
Corresponding Author
Lorenz Trachsel
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Correspondence to: Lorenz Trachsel, as above. E-mail: [email protected]Search for more papers by this authorHans-Ulrich Dodt
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Search for more papers by this authorWalter Zieglgänsberger
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Search for more papers by this authorLorenz Trachsel,
Hans-Ulrich Dodt,
Walter Zieglgänsberger,
Corresponding Author
Lorenz Trachsel
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Correspondence to: Lorenz Trachsel, as above. E-mail: [email protected]Search for more papers by this authorHans-Ulrich Dodt
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Search for more papers by this authorWalter Zieglgänsberger
Max Planck Institute of Psychiatry, Clinical Institute, Clinical Neuropharmacology, Kraepelinstrasse 2, 80804 Munich, Germany
Search for more papers by this authorAbstract
Infrared light transmittance imaging was used in rat hypothalamic slices to record an intrinsic optical signal (IOS) of the cell ensemble in the suprachiasmatic nuclei (SCN), the locus of the endogenous circadian clock. Upon optic chiasm stimulation, a transient IOS was observed in an area conforming to the known retinohypothalamic tract innervation in the ventral SCN. An increase in extracellular Mg2+ concentration to 10 mM reduced the IOS, suggesting that the elicited IOS is dependent on synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and muscimol suppressed the elicited IOS, indicating that NMDA and GABAA receptor-mediated mechanisms were involved in cell ensemble activity reflected in the IOS. The extracellularly recorded spiking of SCN neurons located outside the IOS area remained largely unaffected by the afferent stimulus. Neurons located within the IOS area responded with a depressed electrical discharge, manifesting an inverse relationship between single-unit discharge and the optical measure. The influence of the endogenous circadian rhythm on the elicited IOS was assessed by carrying out daytime-dependent concentration-response experiments. NMDA and non-NMDA receptor specific compounds did not exhibit significant day-night differences, whereas GABA-specific ligands showed a significant day-night variation in activity. The competitive GABAA receptor antagonist bicuculline enhanced the IOS exclusively in the daytime SCN. 5α-Pregnane-3α, 21-diol-20-one (allotetrahydrodeoxy-corticosterone), a neuroactive steroid that potentiates GABAergic inhibition, suppressed the IOS in the night-time SCN more than in the daytime SCN. This suggests that in the rat the level of extracellular GABA is higher in the night-time SCN compared to the daytime SCN.
Abbreviations:
-
- ANOVA
-
- analysis of variance
-
- AMPA
-
- (RS)-α-amino3-hydroxy-5-methyl-4-isoxazolepropionate
-
- CNQX
-
- 6-cyano-7-nitroquinoxaline-2, 3-dione
-
- D-AP5
-
- D-2-amino-5-phosphonopentanoic acid
-
- DMSO
-
- dimethyl sulphoxide
-
- EAA
-
- excitatory amino acid(s)
-
- GABA
-
- γ-aminobutyric acid
-
- IOS
-
- intrinsic optical signal
-
- NMDA
-
- N-methyl-D-aspartate
-
- SCN
-
- suprachiasmatic nuclei
-
- D-SCN
-
- daytime SCN
-
- N-SCN
-
- night-time SCN
-
- 5αTHDOC
-
- 5α-pregnane-3α, 21-diol-20-one (allotetrahydrodeoxycorticosterone)
References
- Aaronin, N., Sagar, S. M., Sharp, F. R. and Schwartz, W. J. (1990) Light regulates expression of a Fos related protein in rat suprachiasmatic nuclei. Proc. Natl Acad. Sci. USA, 87, 5959–5962.
- Abe, H., Rusak, B. and Robertson, H. A. (1992) NMDA and non-NMDA antagonists inhibit photic induction of Fos protein in the hamster suprachiasmatic nucleus. Brain Res. Bull., 28, 831–835.
- Aguilar-Roblero, R., Verduzco-Carbajal, L., Rodriguez, C., Mendez-Franco, J., Moran, J. and De la Mora, M. P. (1993) Circadian rhythmicity in the GABAergic system in the suprachiasmatic nuclei of the rat. Neurosci. Lett., 157, 199–202.
- Andrew, R. D. and Mac Vicar, B. A. (1994) Imaging cell volume changes and neuronal excitation in the hippocampal slice. Neuroscience, 62, 371–383.
- Card, J. P. and Moore, R. Y. (1989) Orginization of the lateral geniculate-hypothalamic connections in the rat. J. Comp. Neurol., 284, 135–147.
- Cahill, G. M. and Menaker, M. (1987) Kynurenic acid blocks suprachiasmatic nucleus responses to optic nerve stimulation. Brain Res., 410, 125–129.
- Cahill, G. M. and Menaker, M. (1989) Effects of excitatory amino acid receptor antagonists and agonists on suprachiasmatic nucleus responses to retinohypothalamic tract volleys. Brain Res., 479, 76–82.
- Cassone, V. M., Speh, J. C., Card, J. P. and Moore, R. Y. (1988) Comparative anatomy of mammalian suprachiasmatic nucleus. J. Biol. Rhythms, 3, 71–91.
- Cohen, L. B., Keynes, R. D. and Landowne, D. (1972) Changes of light scattering that accompany the action potential in squid giant axons: potential-dependent components. J. Physiol. (Lond.), 224, 701–725.
- Deisz, R. A. and Prince, D. A. (1989) Frequency-dependent depression of inhibition in guinea-pig neocortex in vitro by GABAB receptor feedback on GABA release. J. Physiol. (Lond.), 412, 513–541.
- Decavel, C. and Van den Pol, A. N. (1990) GABA: a dominant neurotransmitter in the hypothalamus. J. Comp. Neurol., 302, 1019–1037.
- De Vries, M. J., Nunes Cardozo, B., Van der Want, J., De Wolf, A. and Meijer, J. H. (1993) Glutamate immunoreactivity in terminals of the retinohypothalamic tract of the brown Norwegian rat. Brain Res., 612, 231–237.
- De Vries, M. J., Treep, J. A., De Pauw, E. S. D. and Meijer, J. H. (1994) The effects of electrical stimulation of the optic nerves and anterior optic chiasm on the circadian activity rhythm of the Syrian hamster: involvement of excitatory amino acids. Brain Res., 642, 206–212.
- Ding, J. M., Chen, D., Weber, E. T., Faiman, L. E., Rea, M. A. and Gillette, M. U. (1994) Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science, 266, 1713–1717.
- Dodt, H.-U. and Zieglgänsberger, W. (1990) Visualizing unstained neurons in living brain slices by infrared DIC videomicroscopy. Brain Res., 537, 333–336.
- Dodt, H.-U. and Zieglgänsberger, W. (1994) Infrared videomicroscopy: a new look at neuronal structure and function. Trends Neurosci., 17, 453–458.
- Earnest, D. J. and Sladek, C. S. (1986) Circadian vasopressin release from individual rat suprachiasmatic explants in vitro. Brain Res., 382, 129–133.
- Federico, P., Borg, S. G., Salkauskus, A. G. and Mac Vicar, B. (1994) Mapping patterns of neuronal activity and seizure propagation by imaging intrinsic optical signals in the isolated whole brain of the guinea-pig. Neuroscience, 58, 461–480.
- Frostig, R. D., Lieke, E. E., Ts'o, D. Y. and Grinvald, A. (1990) Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc. Natl Acad. Sci. USA, 87, 6082–6086.
- Gannon, R. L. and Rea, M. A. (1993) Glutamate receptor immunoreactivity in the rat suprachiasmatic nucleus. Brain Res., 622, 337–342.
- Green, D. J. and Gillette, R. (1982) Circadian rhythm of firing rate recorded from single cells in the rat suprachiasmatic brain slice. Brain Res., 245, 198–200.
- Grinvald, A., Manker, A. and Segal, M. (1982) Visualization of the spread of electrical activity in rat hippocampal slices by voltage-sensitive optical probes. J. Physiol. (Lond.), 333, 269–291.
- Groos, G. and Hendricks, J. (1982) Circadian rhythms in electrical discharge of rat suprachiasmatic neurones recorded in vitro. Neuroscience, 34, 283–288.
- Hablitz, J. J. and Heinemann, U. (1989) Alterations in the microenvironment during spreading depression associated with epileptiform activity in the immature neocortex. Dev. Brain Res., 46, 243–252.
- Haglund, M. M., Ojemann, G. A. and Hochman, D. W. (1992) Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature, 358, 668–671.
- Holthoff, K., Dodt, H.-U. and Witte, O. W. (1994) Changes in intrinsic optical signal of rat neocortical slices following afferent stimulation. Neurosci. Lett., 280, 227–230.
- Johnson, R. F., Moore, R. Y. and Morin, L. P. (1988) Retinohypothalamic projections in the rat and hamster demonstrated using cholera toxin. Brain Res., 462, 301–312.
- Kim, Y. I. and Dudek, F. E. (1991) Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: excitatory synaptic mechanisms. J. Physiol. (Lond.), 444, 269–287.
- Kim, Y. I. and Dudek, F. E. (1992) Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: inhibitory synaptic mechanisms. J. Physiol. (Lond.), 458, 247–260.
- Kimelberg, H. K. and Frangakis, M. V. (1985) Furosemide- and bumetanide-sensitive ion transport and volume control in primary astrocyte cultures from rat brain. Brain Res., 361, 125–134.
- Liou, S. Y., Shibata, S., Iwasaki, K. and Ueki, S. (1986) Optic nerve stimulation-induced increase of release of 3H-glutamate and 3H-aspartate but not 3H-GABA from the suprachiasmatic nucleus in slices of rat hypothalamus. Brain Res., 16, 527–531.
- Liou, S. Y., Shibata, S., Albers, H. E. and Ueki, S. (1990) Effects of GABA and anxiolytics on the single unit discharge of suprachiasmatic neurons in rat hypothalamic slices. Brain Res., 25, 103–107.
- Lundberg, J. M. (1991) Volume transmission by coreleased peptides in autonomic nervous system. In K. Fuxe and L. F. Agnati (eds) , Volume Transmission in the Brain: Novel Mechanisms for Neurol Transmission. Raven Press, New York , pp. 425–432.
- MacVicar, B. A. (1984) Infrared video microscopy to visualize neurons in the in vitro brain slice preparation. J. Neurosci. Methods, 12, 133–139.
- MacVicar, B. A. and Hochman, D. (1991) Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J. Neurosci., 11, 1458–1469.
- Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L. and Paul, S. M. (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science, 232, 1004–1007.
- Mason, R. (1986) Circadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat. J. Physiol. (Lond.), 377, 1–13.
- Mason, R., Biello, S. M. and Harrington, M. E. (1991) The effects of GABA and benzodiazepines on neurones in the suprachiasmatic nucleus (SCN) of Syrian hamsters. Brain Res., 552, 53–57.
- Meijer, J. H. and Rietveld, W. J. (1989) Neurophysiology of the suprachiasmatic pacemaker in rodents. Physiol. Rev., 69, 671–707.
- Meijer, J. H., Groos, G. A. and Rusak, B. (1986) Luminance coding in a circadian pacemaker: the suprachiasmatic nucleus of the rat and the hamster. Brain Res., 382, 109–118.
- Meijer, J. H., Van der Zee, E. A. and Dietz, M. (1988) Glutamate phase shifts circadian activity rhythms in hamsters. Neurosci. Lett., 86, 177–183.
- Miller, J. D. (1993) On the nature of the circadian clock in mammals. Am. J. Physiol., 264, R821–R832.
- Moore, R. Y. and Lenn, N. J. (1972) A retinohypothalamic projection in the rat. J. Comp. Neurol., 146, 1–14.
- Moore, R. Y. and Speh, J. C. (1993) GABA is the principal neurotransmitter in the mammalian circadian system. Neurosci. Lett., 150, 112–116.
- Newman, G. C., Hospod, F. E., Patlak, C. S. and Moore, R. Y. (1992) Analysis of in vitro glucose utilization in a circadian pacemaker model. J. Neurosci., 12, 2015–2021.
- Obeidal, A. S., Adams, J. R. and Andrew, R. D. (1994) Imaging intrinsic optical signals associated with brief hypoxia/hypoglycemia in rat hippocampal slice. Soc. Neurosci. Abstr., 20, 180.
- Pérez-Armendariz, M., Roy, C., Spray, D. C. and Bennett, M. V. L. (1991) Biophysical properties of gap-junctions between freshly dispersed pairs of mouse pancreatic beta cells. Biophys. J., 59, 76–92.
- Pickard, G. E. (1982) The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projections. J. Comp. Neurol., 211, 65–83.
- Poe, G. R., Rector, D. M. and Harper, R. M. (1994) Hippocampal reflected optical patterns during sleep and waking states in the freely behaving cat. J. Neurosci., 14, 2933–2942.
- Prosser, R. A. and Gillette, M. U. (1989) The mammalian circadian clock in the suprachiasmatic nuclei is reset in vitro by cAMP. J. Neurosci., 9, 1073–1081.
- Ralph, M. R. and Menaker, M. (1989) GABA regulation of circadian responses to light. I. Involvement of GABAa—benzodiazepine and GABAb receptors. J. Neurosci., 9, 2858–2865.
- Rangarajan, R., Heller, H. C. and Miller, J. D. (1994) Chloride channel block phase advances the single-unit activity rhythm in the SCN. Brain Res. Bull., 34, 69–72.
- Rausche, G., Sarvey, J. M. and Heinemann, U. (1989) Slow synaptic inhibition in relation to frequency habituation in dentate granule cells of rat hippocampal slices. Exp. Brain Res., 78, 233–242.
- Richard, D., Faiman, L. and Gillette, M. U. (1991) Quantitation of glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) in single suprachiasmatic nuclei (SCN) across the circadian cycle. Soc. Neurosci. Abstr., 17, 671.
- Rupprecht, R., Reul, J. M. H. M., Trapp, T., van Steensel, B., Wetzel, C., Damm, K., Zieglgänsberger, W. and Holsboer, F. (1993) Progesterone receptor-mediated effects of neuroactive steroids. Neuron, 11, 523–530.
- Rusak, B. (1989) The mammalian circadian system: models and physiology. J. Biol. Rhythms, 4, 121–1340.
- Rusak, B., Robertson, H. A., Wisden, W. and Hunt, S. P. (1993) Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. Science, 248, 1237–1240.
- Schwartz, W. J., Davidsen, L. C. and Smith, C. B. (1980) In vivo metabolic activity of a putative circadian oscillator, the rat suprachiasmatic nucleus. J. Comp. Neurol., 189, 157–167.
- Senseman, D. M. and Rea, M. A. (1994) Fast multisite optical recording of mono- and polysynaptic activity in the hamster suprachiasmatic nucleus evoked by retinohypothalamic tract stimulation. Neuroimage, 1, 247–263.
- Shibata, S., Oomura, Y., Kita, H. and Hattori, K. (1982) Circadian rhythmic changes of neuronal activity in the suprachiasmatic nucleus of the rat hypothalamic slice. Brain Res., 247, 154–157.
- Shibata, S., Oomura, Y., Hattori, K. and Kita, H. (1984) Responses of suprachiasmatic nucleus neurons to optic nerve stimulation in rat hypothalamic slice preparation. Brain Res., 302, 83–89.
- Shibata, S., Liou, S. Y. and Ueki, S. (1986) Influence of excitatory amino acid receptor antagonists and of baclofen on synaptic transmission in the optic nerve to the suprachiasmatic nucleus in slices of rat hypothalamus. Neuropharmacology, 25, 403–409.
- Shirakawa, T. and Moore, R. Y. (1994) Responses of rat suprachiasmatic nucleus neurons to substance P and glutamate in vitro. Brain Res., 642, 213–220.
- Smith, R. D., Turek, F. W. and Slater, N. T. (1990) Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen-insensitive mechanism. Brain Res., 530, 275–282.
- Teschemacher, A., Zeise, M. L., Holsboer, F. and Zieglgänsberger, W. (1995) The neuroactive steroid 5α-tetrahydrodeoxycorticosterone increases GABAergic postsynaptic inhibition in rat neocortical neurons in vitro. J. Neuroendocrinol., 7, 233–240.
- Tominaga, K., Shibata, S., Hamada, T. and Watanabe, S. (1994) GABA-A receptor agonist muscimol can reset the phase of neural activity rhythm in the rat suprachiasmatic nucleus in vitro. Neurosci. Lett., 166, 81–84.
- Trachsel, L., Dodt, H.-U. and Zieglgänsberger, W. (1993) Optical recordings with infrared dark-field microscopy in hypothalamic slices containing the suprachiasmatic nuclei. Soc. Neurosci. Abstr., 19, 1056.
- Trachsel, L., Heller, H. C. and Miller, J. D. (1995) Nicotine phase-advances the circadian neuronal activity rhythm in rat suprachiasmatic nuclei explants. Neuroscience, 65, 797–803.
- Ts'o, D. Y., Frostig, R. D., Lieke, E. E. and Grinvald, A. (1990) Functional organization of primate visual cortex revealed by high resolution optical imaging. Science, 249, 417–420.
- Van den Pol, A. N. (1991) Glutamate and aspartate immunoreactivity in hypothalamic presynaptic axons. J. Neurosci., 11, 2087–2101.
- Van den Pol, A. N., Finkbeiner, S. M. and Cornell-Bell, A. H. (1992) Calcium excitability and oscillations in suprachiasmatic nucleus neurons and glia in vitro. J. Neurosci., 12, 2648–2664.
- Vindlacheruvu, R. R., Ebling, F. J. P., Maywood, E. S. and Hastings, M. H. (1992) Blockade of glutamatergic neurotransmission in the suprachiasmatic nucleus prevents cellular and behavioural responses of the circadian system to light. Eur. J. Neurosci., 4, 673–679.
- Wetzel, C. H. R., Deisz, R. A., Vedder, H. and Zieglgänsberger, W. (1995) Modulatory effects of the neuroactive steroid THDOC on GABA-induced chloride currents in cultured rat hypothalamic neurons. Soc. Neurosci. Abstr., 21, 1025.
