Cation-chloride cotransporters and the polarity of GABA signaling 2 in mouse hippocampal parvalbumin interneurons Running title: GABA signaling in hippocampal parvalbumin interneurons - Sorbonne Université
Preprints, Working Papers, ... Year : 2020

Cation-chloride cotransporters and the polarity of GABA signaling 2 in mouse hippocampal parvalbumin interneurons Running title: GABA signaling in hippocampal parvalbumin interneurons

Abstract

Transmembrane chloride gradients govern the efficacy and polarity of GABA signaling in neurons and are usually maintained by the activity of cation chloride cotransporters, such as KCC2 and NKCC1. Whereas their role is well established in cortical principal neurons, it remains poorly documented in GABAergic interneurons. We used complementary electrophysiological approaches to compare the effects of GABAAR activation in adult mouse hippocampal parvalbumin interneurons (PV INs) and pyramidal cells (PCs). Loose cell attached, tight-seal and gramicidin-perforated patch recordings all show GABAAR-mediated transmission is slightly depolarizing and yet inhibitory in both PV INs and PCs. Focal GABA uncaging in whole-cell recordings reveal that KCC2 and NKCC1 are functional in both PV INs and PCs but differentially contribute to transmembrane chloride gradients in their soma and dendrites. Blocking KCC2 function depolarizes the reversal potential of GABAAR-mediated currents in PV INs and PCs, often beyond firing threshold, showing KCC2 is essential to maintain the inhibitory effect of GABAARs. Finally, we show that repetitive 10 Hz activation of GABAARs in both PV INs and PCs leads to a progressive decline of the postsynaptic response independently of the ion flux direction or KCC2 function. This suggests intraneuronal chloride buildup may not predominantly contribute to activity-dependent plasticity of GABAergic synapses in this frequency range. Altogether our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal PV INs and PCs and suggest KCC2 downregulation in the pathology may affect the valence of GABA signaling in both cell types.
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Dates and versions

hal-02985908 , version 1 (02-11-2020)

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Yo Otsu, Florian Donneger, Eric J Schwartz, Jean Christophe Poncer. Cation-chloride cotransporters and the polarity of GABA signaling 2 in mouse hippocampal parvalbumin interneurons Running title: GABA signaling in hippocampal parvalbumin interneurons. 2020. ⟨hal-02985908⟩
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