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Astrocyte-mediated potentiation of inhibitory synaptic transmission

Abstract

We investigated the role of astrocytes in activity-dependent modulation of inhibitory synaptic transmission in hippocampal slices. Repetitive firing of an interneuron decreased the probability of synaptic failures in spike-evoked inhibitory postsynaptic currents (unitary IPSCs) in CA1 pyramidal neurons. The GABA B -receptor antagonist CGP55845A abolished this effect. Direct stimulation of astrocytes, or application of the GABA B -receptor agonist baclofen, potentiated miniature inhibitory postsynaptic currents (mIPSCs) in pyramidal neurons. These effects were blocked by inhibition of astrocytic calcium signaling with the calcium chelator BAPTA or by antagonists of the ionotropic glutamate receptors. These observations suggest that interneuronal firing elicits a GABA B -receptor-mediated elevation of calcium in surrounding astrocytes, which in turn potentiates inhibitory transmission. Astrocytes may therefore be a necessary intermediary in activity-dependent modulation of inhibitory synapses in the hippocampus.

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Figure 1: Identification of pyramidal neurons, interneurons and astrocytes in hippocampal slices.
Figure 2: Activity-dependent modulation of inhibitory synaptic transmission.
Figure 3: Increase in miniature inhibitory postsynaptic currents (mIPSCs) induced by astrocyte stimulation in hippocampal CA1 pyramidal neurons.
Figure 4: Astrocytic calcium signaling is required for the increase in mIPSCs.
Figure 5: The ionotropic glutamate receptor antagonists CNQX and AP5 blocked the increase in mIPSCs induced by astrocyte stimulation.
Figure 6: Stimulation of an interneuron elicits calcium elevations in surrounding astrocytes.
Figure 7: GABAB receptors mediate interactions between interneurons and astrocytes.
Figure 8: Baclofen-induced increase in mIPSCs.

References

  1. Bliss, T. V. P. & Gardner-Medwin, A. R. Long-lasting potentiation of synaptic transmission in the dentate area of the unaesthetized rabbit following stimulation of the perforant path. J. Physiol. (Lond.) 232, 357–374 ( 1973).

    CAS  Article  Google Scholar 

  2. Bliss, T. V. P. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 ( 1993).

    CAS  Article  Google Scholar 

  3. Malenka, R. C. & Nicoll, R. A. NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci. 16, 521–527 (1993).

    CAS  Article  Google Scholar 

  4. Korn, H., Oda, Y. & Faber, D. S. Long-term potentiation of inhibitory circuits and synapses in the central nervous system. Proc. Natl. Acad. Sci. USA 89, 440–443 (1992).

    CAS  Article  Google Scholar 

  5. Kano, M., Rexhausen, U., Dreessen, J. & Konnerth, A. A. Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356, 601–604 (1992).

    CAS  Article  Google Scholar 

  6. Komatsu, Y. Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex. J. Neurosci. 14, 6488 –6499 (1994).

    CAS  Article  Google Scholar 

  7. Xie, Z., Yip, S., Morishita, W. & Sastry, B. R. Tetanus-induced potentiation of inhibitory postsynaptic potentials in hippocampal CA1 neurons. Can. J. Physiol. Pharmacol. 73, 1706– 1713 (1995).

    CAS  Article  Google Scholar 

  8. Wong, R. K. S. & Watkins, D. J. Cellular factors influencing GABA response in hippocampal pyramidal cells. J. Neurophysiol. 48, 938–951 ( 1982).

    CAS  Article  Google Scholar 

  9. Thompson, S. M. & Gähwiler, B. H. Activity-dependent disinhibition I. Repetitive stimulation reduces IPSP driving force and conductance in the hippocampus in vitro. J. Neurophysiol. 61, 501–511 (1989).

    CAS  Article  Google Scholar 

  10. McCarren, M. & Alger, B. E. Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro. J. Neurophysiol. 53, 557–571 (1985).

    CAS  Article  Google Scholar 

  11. Cox, C. L., Huguenard, J. R. & Prince, D. A. Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus. Proc. Natl. Acad. Sci. USA 94, 8854–8859 (1997).

    CAS  Article  Google Scholar 

  12. Stuart, G. J. & Sakmann, B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367, 69–72 (1994).

    CAS  Article  Google Scholar 

  13. Pouzat, C. & Hestrin, S. Developmental regulation of basket/stellate cell→Purkinje cell synapses in the cerebellum. J. Neurosci. 17, 9104–9112 ( 1997).

    CAS  Article  Google Scholar 

  14. Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S. & Smith, S. J. Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247, 470–473 (1990).

    CAS  Article  Google Scholar 

  15. Dani, J. W., Chernjavsky, A. & Smith, S. J. Neuronal activity triggers calcium waves in hippocampal astrocyte networks. Neuron 8, 429– 440 (1992).

    CAS  Article  Google Scholar 

  16. Porter, J. T. & McCarthy, K. D. Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J. Neurosci. 16, 5073–5081, 1996.

    CAS  Article  Google Scholar 

  17. Nedergaard, M. Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263, 1768– 1771 (1994).

    CAS  Article  Google Scholar 

  18. Parpura, V. et al. Glutamate-mediated astrocyte-neuron signaling. Nature 369, 744–747 ( 1994).

    CAS  Article  Google Scholar 

  19. Pasti, L., Volterra, A., Pozzan, T. & Carmignoto, G. Intracellular calcium oscillations in astrocytes: A highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J. Neurosci. 17, 7817–7830 (1997).

    CAS  Article  Google Scholar 

  20. Araque, A., Parpura, V., Sanzgiri, R. P. & Hayton, P. G. Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur. J. Neurosci. 10, 2129–2142 (1998).

    CAS  Article  Google Scholar 

  21. Newman, E. A. & Zahs, K. R. Modulation of neuronal activity by glial cells in the retina. J. Neurosci. 18, 4022–4028 (1998).

    CAS  Article  Google Scholar 

  22. Cotrina, M. L. et al. Astrocytic gap junctions remain open during ischemic conditions. J. Neurosci. 18, 2520– 2537 (1998).

    CAS  Article  Google Scholar 

  23. Thompson, S. M., Masukawa, L. M. & Prince, D. A. Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro. J. Neurosci. 5, 817–824 ( 1985).

    CAS  Article  Google Scholar 

  24. Miles, R. Tetanic stimuli induce a short-term enhancement of recurrent inhibition in the CA3 region of guinea-pig hippocampus in vitro. J. Physiol. (Lond.) 443, 669–682 ( 1991).

    CAS  Article  Google Scholar 

  25. Fleidervish, I. A. & Gutnick, M. J. Paired-pulse facilitation of IPSCs in slices of immature and mature mouse somatosensory neocortex. J. Neurophysiol. 73, 2591– 2595 (1995).

    CAS  Article  Google Scholar 

  26. Jeftinija, S. D., Jeftinija, K. V., Stefanovic, G. & Liu, F. Neuroligand-evoked calcium-dependent release of excitatory amino acids from cultured astrocytes. J. Neurochem. 66, 676 –684 (1996).

    CAS  Article  Google Scholar 

  27. Bezzi, P. et al. Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391, 281– 285 (1998).

    CAS  Article  Google Scholar 

  28. Nilsson, M., Eriksson, P. S., Rönnbäck, L. & Hansson, E. GABA induces Ca2+ transients in astrocytes. Neuroscience 54, 605–614 ( 1993).

    CAS  Article  Google Scholar 

  29. Davies, C. H. & Collingridge, G. L. The physiological regulation of synaptic inhibition by GABAB autoreceptors in rat hippocampus. J. Physiol. (Lond.) 472, 245– 265 (1993).

    CAS  Article  Google Scholar 

  30. Miles, R., Tóth, K., Gulyás, A. I., Hájos, N. & Freund, T. F. Differences between somatic and dendritic inhibition in the hippocampus. Neuron 16, 815–823 ( 1996).

    CAS  Article  Google Scholar 

  31. Frerking, M., Borges, S. & Wilson, M. Variation in GABA mini amplitude is the consequence of variation in transmitter concentration. Neuron 15 , 885–895 (1995).

    CAS  Article  Google Scholar 

  32. Korn, S. J., Giacchino, J. L., Chamberlin, N. L. & Dingledine, R. Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. J. Neurophysiol. 57, 325–341 (1987).

    CAS  Article  Google Scholar 

  33. Kang, J., Huguenard, J. R. & Prince, D. A. Postnatal development of BK channels in rat neocortical pyramidal neurons. J. Neurophysiol. 76, 188–198 (1996).

    CAS  Article  Google Scholar 

  34. Hamill, O. P., Marty, A., Neher, E., Sackmann, B. & Sigworth, B. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch. 391, 85–100 ( 1981).

    CAS  Article  Google Scholar 

  35. Lin, J. C. et al. Gap-junction-mediated propagation and amplification of cell injury. Nature Neurosci. 1, 494– 500 (1998).

    CAS  Article  Google Scholar 

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Acknowledgements

We thank David A. Prince, John R. Huguenard, Zixiu Xiang, Juan C. López and William N. Ross for suggestions. This work was sponsored by NIDH/NIH IR29NS37349-01, RO1NS30007, RO1NS35011, RO1NS29813, RO1NS33106, Mathers Charitable Foundation and The Alexandrine & Alexander L. Sinsheimer Scholar Award.

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Correspondence to Jian Kang.

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Kang, J., Jiang, L., Goldman, S. et al. Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat Neurosci 1, 683–692 (1998). https://doi.org/10.1038/3684

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