| First Author | Leonzino M | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 1 | Pages | 96-103 |
| PubMed ID | 27052180 | Mgi Jnum | J:235079 |
| Mgi Id | MGI:5792759 | Doi | 10.1016/j.celrep.2016.03.013 |
| Citation | Leonzino M, et al. (2016) The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2. Cell Rep 15(1):96-103 |
| abstractText | 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. |
