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.
The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 / M. Leonzino, M. Busnelli, F. Antonucci, C. Verderio, M. Mazzanti, B. Chini. - In: CELL REPORTS. - ISSN 2211-1247. - 15:1(2016 Apr), pp. 96-103.
|Titolo:||The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2|
LEONZINO, MARIANNA (Primo)
MAZZANTI, MICHELE (Penultimo)
|Parole Chiave:||biochemistry; genetics and molecular biology (all)|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/09 - Fisiologia
|Data di pubblicazione:||apr-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.celrep.2016.03.013|
|Appare nelle tipologie:||01 - Articolo su periodico|