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 Repjournal_title
Cell reportsauthors
Leonzino M,Busnelli M,Antonucci F,Verderio C,Mazzanti M,Chini Bdoi
10.1016/j.celrep.2016.03.013subject
Has Abstractpub_date
2016-04-05 00:00:00pages
96-103issue
1issn
2211-1247pii
S2211-1247(16)30254-6journal_volume
15pub_type
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