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Astrocyte-mediated potentiation of inhibitory synaptic transmission

Nature Neuroscience volume 1, pages 683–692 (1998)Cite this article

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.

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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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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, New York Medical College, Basic Science Building, Room 204, Valhalla, 10595, New York, USA

    Jian Kang, Li Jiang & Maiken Nedergaard

  2. Department of Neurology and Neuroscience, Cornell University Medical College, New York, 10021, New York, USA

    Steven A. Goldman

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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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