Skip to Main content Skip to Navigation
Journal articles

Cation-chloride cotransporters and the polarity of GABA signalling in mouse hippocampal parvalbumin interneurons

Abstract : KEY POINTS: Cation-chloride cotransporters (CCCs) play a critical role in controlling the efficacy and polarity of GABAA receptor (GABAAR)-mediated transmission in the brain, yet their expression and function in GABAergic interneurons has been overlooked. We compared the polarity of GABA signalling and the function of CCCs in mouse hippocampal pyramidal neurons and parvalbumin-expressing interneurons. Under resting conditions, GABAAR activation was mostly depolarizing and yet inhibitory in both cell types. KCC2 blockade further depolarized the reversal potential of GABAAR-mediated currents often above action potential threshold. However, during repetitive GABAAR activation, the postsynaptic response declined independently of the ion flux direction or KCC2 function, suggesting intracellular chloride buildup is not responsible for this form of plasticity. Our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal pyramidal neurons and parvalbumin interneurons. ABSTRACT: Transmembrane chloride gradients govern the efficacy and polarity of GABA signalling 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 signalling in both cell types.
Complete list of metadatas

Cited literature [101 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02472553
Contributor : Jean Christophe Poncer <>
Submitted on : Monday, February 10, 2020 - 12:17:53 PM
Last modification on : Friday, April 17, 2020 - 2:56:03 PM
Long-term archiving on: : Monday, May 11, 2020 - 2:37:07 PM

File

Otsu et al R2final.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Yo Otsu, Florian Donneger, Eric Schwartz, Jean Poncer. Cation-chloride cotransporters and the polarity of GABA signalling in mouse hippocampal parvalbumin interneurons. The Journal of Physiology, Wiley, 2020, Epub ahead of print. ⟨10.1113/JP279221⟩. ⟨inserm-02472553⟩

Share

Metrics

Record views

118

Files downloads

50