A Cellular Mechanism of Learning-Induced Enhancement of Synaptic Inhibition: PKC-Dependent Upregulation of KCC2 Activation

Adi Kfir, Richa Awasthi, Sourav Ghosh, Sankhanava Kundu, Blesson Paul, Raphael Lamprecht, Edi Barkai

Research output: Contribution to journalArticlepeer-review

Abstract

Long-term memory of complex olfactory learning is expressed by wide spread enhancement in excitatory and inhibitory synaptic transmission onto piriform cortex pyramidal neurons. A particularly interesting modification in synaptic inhibition is the hyperpolarization of the reversal potential of the fast post synaptic inhibitory potential (fIPSP). Here we study the mechanism underlying the maintenance of such a shift in the fIPSP. Blocking of the neuronal specific K+-Cl co-transporter (KCC2) in neurons of trained rats significantly depolarized the averaged fIPSP reversal potential of the spontaneous miniature inhibitory post synaptic currents (mIPSCs), to the averaged pre-training level. A similar effect was obtained by blocking PKC, which was previously shown to upregulate KCC2. Accordingly, the level of PKC-dependent phosphorylation of KCC2, at the serine 940 site, was significantly increased after learning. In contrast, blocking two other key second messenger systems CaMKII and PKA, which have no phosphorylation sites on KCC2, had no effect on the fIPSP reversal potential. Importantly, the PKC inhibitor also reduced the averaged amplitude of the spontaneous miniature excitatory synaptic currents (mEPSCs) in neurons of trained rats only, to the pre-training level. We conclude that learning-induced hyper-polarization of the fIPSP reversal potential is mediated by PKC-dependent increase of KCC2 phosphorylation.

Original languageEnglish
Article number962
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
The research is supported by a grant from the Israel Academy of Sciences and Humanities awarded to EB.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • General

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