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. [10.1016/j.celrep.2016.03.013]

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

M. Leonzino
Primo
;
F. Antonucci;M. Mazzanti
Penultimo
;
2016

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.
biochemistry; genetics and molecular biology (all)
Settore BIO/14 - Farmacologia
Settore BIO/09 - Fisiologia
apr-2016
Article (author)
File in questo prodotto:
File Dimensione Formato  
Leonzino et al 2016 Cell Reports.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 2.87 MB
Formato Adobe PDF
2.87 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/440131
Citazioni
  • ???jsp.display-item.citation.pmc??? 66
  • Scopus 126
  • ???jsp.display-item.citation.isi??? 101
social impact