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Publication Detail
Presynaptic GABAA receptors enhance glutamatergic transmission and facilitate LTP induction at hippocampal mossy fibre synapses
  • Publication Type:
  • Authors:
    Ruiz AJ, Campanac E, Scott R, Rusakov D, Kullmann D
  • Presented date:
  • Presented at:
    7th FENS Forum of European Neuroscience
  • Location:
    RAI Convention Centre, Amsterdam, The Netherlands
  • Addresses:
    School of Pharmacy
    Brunswick Square
    WC1N 1AX
    United Kingdom

    Institute of Neurology
    Queen Square
    WC1N 3BG
    United Kingdom

    Instituto de Neurociencias
    Universidad Miguel Hernandez
Presynaptic GABAA receptors occur at hippocampal mossy fibres where they modulate axonal excitability and action potential-dependent Ca2+ transients in individual varicosities. How they modulate neurotransmitter release to postsynaptic targets in CA3 is however poorly understood. We obtained direct patch-clamp recordings from mossy fibre boutons, CA3 pyramidal neurons and interneurones held in voltage-clamp in rat hippocampal slices (postnatal days 21 to 35). We also measured presynaptic action potential-dependent Ca2+ transients in large mossy fibre boutons using 2-photon laser scanning microscopy. We showed that allosteric modulators selective for high-affinity delta-subunit-containing GABAA receptors depolarize mossy fibre boutons, enhance action potential-dependent Ca2+ transients, and facilitate glutamatergic transmission to CA3 pyramidal neurons and stratum lucidum interneurones. Conversely, blocking GABAA receptors with the competitive receptor antagonist gabazine hyperpolarized mossy fibre boutons, increased their input resistance, decreased spike width, and attenuated action potential-dependent presynaptic Ca2+ transients. These results indicate that a subset of presynaptic GABA receptors is tonically active in the absence of added GABA and in conditions where uptake mechanisms are functional. Blocking GABAA receptors also impaired the induction of long-term potentiation at mossy fibre - CA3 synapses, presumably via a presynaptic action. Thus, presynaptic GABAA receptors facilitate synaptic transmission to the hippocampus both directly and by enhancing LTP.
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