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Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses

Abstract

Changes in synaptic efficacy are essential for neuronal development1, learning and memory formation2 and for pathological states of neuronal excitability, including temporal-lobe epilepsy3. At synapses, where there is a high probability of opening of postsynaptic receptors4, all of which are occupied by the released transmitter5,6,7,8,9, the most effective means of augmenting postsynaptic responses is to increase the number of receptors2,10,11. Here we combine quantal analysis of evoked inhibitory postsynaptic currents with quantitative immunogold localization of synaptic GABAA receptors in hippocampal granule cells in order to clarify the basis of inhibitory synaptic plasticity induced by an experimental model of temporal-lobe epilepsy (a process known as kindling)10. We find that the larger amplitude (66% increase) of elementary synaptic currents (quantal size) after kindling results directly from a 75% increase in the number of GABAA receptors at inhibitory synapses on somata and axon initial segments. Receptor density was up by 34–40% and the synaptic junctional area was expanded by 31%. Presynaptic boutons were enlarged, which may account for the 39% decrease in the average number of released transmitter packets (quantal content). Our findings establish the postsynaptic insertion of new GABAA receptors and the corresponding increase in postsynaptic responses augmenting the efficacy of mammalian inhibitory synapses.

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Figure 1: Increased quantal size of eIPSCs in kindled granule cells.
Figure 2: GABAA receptor (β2/3 subunits) immunoreactivity in somatic synapses of granule cells from rats.
Figure 3: Kindling increases the immunoreactive β2/3 subunit content of AIS synapses.
Figure 4: Distribution of synaptic parameters.

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Acknowledgements

We thank Zahida Ahmad and Brian Oyama for excellent technical assistance, Paul Jays for assistance with the photography, Jean-Marc Fritschy for kindly providing the α2, β2/3 and γ2 subunit-selective antibodies, and Werner Sieghart for the α1 subunit-selective antibody. This study was supported by the Medical Research Council (UK), a European Commission Shared Cost RTD Programme Grant (no. BIO4CT96-0585) and NIH grant NS36142.

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Correspondence to Istvan Mody.

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Nusser, Z., Hájos, N., Somogyi, P. et al. Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses. Nature 395, 172–177 (1998). https://doi.org/10.1038/25999

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