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Activity-dependent scaling of GABAergic excitation by dynamic Cl− changes in Cajal–Retzius cells

  • Neuroscience
  • Published:
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Abstract

To unravel the functional implications of activity-dependent Cl− changes during early stages of neuronal development, we determined which changes in the GABA reversal potential (E GABA) and GABAergic rheobase shifts were induced by episodes of GABAA receptor activation using gramicidin-perforated patch-clamp recordings from Cajal–Retzius cells in tangential cortical slices of newborn mice. Under this condition, focal application of the GABAA agonist muscimol (10 μM) depolarized the membrane by 15 ± 0.8 mV (n = 35). Such subthreshold GABAergic depolarizations considerably reduced the rheobase, corresponding to an excitatory action. After repetitive focal muscimol applications (50 pulses at 0.5 Hz) a significant reduction of E GABA and an attenuation of the excitatory GABAergic rheobase shift were observed, while the GABAergic membrane conductance and the absolute value of the rheobase were unaltered after the muscimol pulses. Bath application of 100 μM carbachol induced bursts of spontaneous GABAergic postsynaptic potentials. Both, E GABA and the excitatory GABAergic rheobase shift was significantly reduced after such barrage of carbachol-induced GABAergic postsynaptic potentials, while neither the GABAergic membrane conductance nor the absolute value of the rheobase was affected under this condition. Both results indicate that GABAergic activity itself can limit the excitatory effects of GABAA receptor activation, which supports the hypothesis that the low capacity of the Cl− homeostasis in immature neurons could be a substrate for synaptic scaling and homeostatic plasticity.

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Acknowledgments

This work was supported by a grant from the Deutsche Forschungsgemeinschaft to WK (DFG Ki 835/2). The authors thank B. Krumm for excellent technical work and K. Achilles for her contribution to some experiments. All authors declare that they have no conflicts of interest and state that all experiments comply with the current laws of the country in which they were performed.

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  1. Institute of Physiology and Pathophysiology, University Medical Center Mainz, Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany

    Sergey N. Kolbaev, Heiko J. Luhmann & Werner Kilb

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  1. Sergey N. Kolbaev
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  2. Heiko J. Luhmann
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  3. Werner Kilb
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Correspondence to Werner Kilb.

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Kolbaev, S.N., Luhmann, H.J. & Kilb, W. Activity-dependent scaling of GABAergic excitation by dynamic Cl− changes in Cajal–Retzius cells. Pflugers Arch - Eur J Physiol 461, 557–565 (2011). https://doi.org/10.1007/s00424-011-0935-4

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  • DOI: https://doi.org/10.1007/s00424-011-0935-4

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