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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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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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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