The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2.

Abstract:

:Oxytocin and its receptor (Oxtr) play a crucial role in the postnatal transition of neuronal GABA neurotransmission from excitatory to inhibitory, a developmental process known as the GABA switch. Using hippocampal neurons from Oxtr-null mice, we show that (1) Oxtr is necessary for the correct timing of the GABA switch by upregulating activity of the chloride cotransporter KCC2, (2) Oxtr, in a very early and narrow time window, directly modulates the functional activity of KCC2 by promoting its phosphorylation and insertion/stabilization at the neuronal surface, and (3) in the absence of Oxtr, electrophysiological alterations are recorded in mature neurons, a finding consistent with a reduced level of KCC2 and increased susceptibility to seizures observed in adult Oxtr-null mice. These data identify KCC2 as a key target of oxytocin in postnatal events that may be linked to pathogenesis of neurodevelopmental disorders.

journal_name

Cell Rep

journal_title

Cell reports

authors

Leonzino M,Busnelli M,Antonucci F,Verderio C,Mazzanti M,Chini B

doi

10.1016/j.celrep.2016.03.013

subject

Has Abstract

pub_date

2016-04-05 00:00:00

pages

96-103

issue

1

issn

2211-1247

pii

S2211-1247(16)30254-6

journal_volume

15

pub_type

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