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Presynaptic GABAA receptors enhance transmission and LTP induction at hippocampal mossy fiber synapses

Nature Neuroscience volume 13, pages 431–438 (2010)Cite this article

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Abstract

Presynaptic GABAA receptors (GABAARs) occur at hippocampal mossy fiber synapses. Whether and how they modulate orthodromic signaling to postsynaptic targets is poorly understood. We found that an endogenous neurosteroid that is selective for high-affinity δ subunit–containing GABAARs depolarized rat mossy fiber boutons, enhanced action potential–dependent Ca2+ transients and facilitated glutamatergic transmission to pyramidal neurons. Conversely, blocking GABAARs hyperpolarized mossy fiber boutons, increased their input resistance, decreased spike width and attenuated action potential–dependent presynaptic Ca2+ transients, indicating that a subset of presynaptic GABA receptors are tonically active. Blocking GABAARs also interfered with the induction of long-term potentiation at mossy fiber–CA3 synapses. Presynaptic GABAARs therefore facilitate information flow to the hippocampus both directly and by enhancing LTP.

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Figure 1: THDOC modulates GABAA receptors in outside-out patches from mossy fiber boutons.
Figure 2: Noninvasive measurement of mossy fiber membrane potential and modulation via GABAA receptors.
Figure 3: Blocking GABAA receptors reveals a tonic current in mossy fiber boutons.
Figure 4: Tonic GABAA receptor–mediated currents modulate the electrical properties of mossy fiber boutons.
Figure 5: Tonically active neurosteroid-sensitive GABAA receptors enhance presynaptic action potential–dependent Ca2+ transients in giant mossy fiber boutons.
Figure 6: Bidirectional modulation of synaptic transmission via tonically active GABAA receptors at mossy fibers.
Figure 7: GABAA receptors facilitate mossy fiber LTP.

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Acknowledgements

We are grateful to P. Jonas and to D. Engel for help in optimizing mossy fiber bouton recordings and to C. Henneberger, M.C. Walker and K. Volynski for comments on the manuscript. This work was supported by the Medical Research Council (UK), the Wellcome Trust, the European Research Council and the Fondation pour la Recherche Médicale (France).

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Author notes

  1. Ricardo S Scott

    Present address: Present address: Instituto de Neurociencias, CSIC & Universidad Miguel Hernández, Alicante, Spain.,

  2. Emilie Campanac and Ricardo S Scott: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Neurology, University College London, London, UK

    Arnaud Ruiz, Emilie Campanac, Ricardo S Scott, Dmitri A Rusakov & Dimitri M Kullmann

  2. Department of Pharmacology, School of Pharmacy, University of London, London, UK

    Arnaud Ruiz

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Contributions

A.R., E.C. and R.S.S. conducted the experiments. A.R. and E.C. analyzed the electrophysiology and epifluorescence imaging data. R.S.S. and D.A.R. analyzed the multi-photon imaging data. A.R., R.S.S., D.A.R. and D.M.K. conceived the study. D.M.K. wrote the first draft of the manuscript, which was revised by all of the authors.

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Correspondence to Arnaud Ruiz or Dimitri M Kullmann.

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Ruiz, A., Campanac, E., Scott, R. et al. Presynaptic GABAA receptors enhance transmission and LTP induction at hippocampal mossy fiber synapses. Nat Neurosci 13, 431–438 (2010). https://doi.org/10.1038/nn.2512

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