The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2
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 timin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716302546 |
| _version_ | 1818301878001205248 |
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| author | Marianna Leonzino Marta Busnelli Flavia Antonucci Claudia Verderio Michele Mazzanti Bice Chini |
| author_facet | Marianna Leonzino Marta Busnelli Flavia Antonucci Claudia Verderio Michele Mazzanti Bice Chini |
| author_sort | Marianna Leonzino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T05:30:00Z |
| format | Article |
| id | doaj.art-4450bdee4def477b8e42b663395e5ef8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T05:30:00Z |
| publishDate | 2016-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4450bdee4def477b8e42b663395e5ef82022-12-21T23:58:06ZengElsevierCell Reports2211-12472016-04-011519610310.1016/j.celrep.2016.03.013The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2Marianna Leonzino0Marta Busnelli1Flavia Antonucci2Claudia Verderio3Michele Mazzanti4Bice Chini5Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan 20129, ItalyInstitute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan 20129, ItalyDepartment of Biotechnology and Translational Medicine, University of Milan, Milan 20129, ItalyInstitute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan 20129, ItalyDepartment of Bioscience, University of Milan, Milan 20133, ItalyInstitute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan 20129, ItalyOxytocin 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.http://www.sciencedirect.com/science/article/pii/S2211124716302546 |
| spellingShingle | Marianna Leonzino Marta Busnelli Flavia Antonucci Claudia Verderio Michele Mazzanti Bice Chini The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 Cell Reports |
| title | The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 |
| title_full | The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 |
| title_fullStr | The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 |
| title_full_unstemmed | The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 |
| title_short | The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2 |
| title_sort | timing of the excitatory to inhibitory gaba switch is regulated by the oxytocin receptor via kcc2 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716302546 |
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