Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance

Tayfun Ates; Merve Oncul; Pelin Dilsiz; Iskalen Cansu Topcu; Cihan Civan Civas; Muhammed Ikbal Alp; Iltan Aklan; Edanur Ates Oz; Yavuz Yavuz; Bayram Yilmaz; Nilufer Sayar Atasoy; Deniz Atasoy

doi:10.1016/j.nbd.2018.09.017

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Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance

Journal article

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Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance

Tayfun Ates, Merve Oncul, Pelin Dilsiz, Iskalen Cansu Topcu, Cihan Civan Civas, Muhammed Ikbal Alp, Iltan Aklan, Edanur Ates Oz, Yavuz Yavuz, Bayram Yilmaz, …

Neurobiology of disease, Vol.121, pp.58-64

01/2019

DOI: 10.1016/j.nbd.2018.09.017

PMID: 30240706

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https://doaj.org/article/8417be2b48e749aaaacca7a05288ce8aView

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Abstract

Prader-Willi and the related Schaaf-Yang Syndromes (PWS/SYS) are rare neurodevelopmental disorders characterized by overlapping phenotypes of high incidence of autism spectrum disorders (ASD) and neonatal feeding difficulties. Based on clinical and basic studies, oxytocin pathway defects are suggested to contribute disease pathogenesis but the mechanism has been poorly understood. Specifically, whether the impairment in oxytocin system is limited to neuropeptide levels and how the functional properties of broader oxytocin neuron circuits affected in PWS/SYS have not been addressed. Using cell type specific electrophysiology, we investigated basic synaptic and cell autonomous properties of oxytocin neurons in the absence of MAGEL2; a hypothalamus enriched ubiquitin ligase regulator that is inactivated in both syndromes. We observed significant suppression of overall ex vivo oxytocin neuron activity, which was largely contributed by altered synaptic input profile; with reduced excitatory and increased inhibitory currents. Our results suggest that dysregulation of oxytocin system goes beyond altered neuropeptide expression and synaptic excitation inhibition imbalance impairs overall oxytocin pathway function. •Loss of Prader-Willi syndrome gene-Magel2 suppresses activity of oxytocin neurons.•Magel2 deficient oxytocin neurons have normal basic membrane properties.•Loss of Magel2 alters excitatory/inhibitory synaptic balance onto oxytocin neurons.•Magel2 mutant oxytocin neurons have selective loss of AMPA but normal NMDA currents.

Autism

AMPA

Oxytocin

NMDA

Electrophysiology

Prader Willi Syndrome

magel2

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Title: Subtitle: Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance
Creators: Tayfun Ates - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Merve Oncul - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Pelin Dilsiz - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Iskalen Cansu Topcu - Department of Physiology, School of Medicine, Yeditepe University, Istanbul, Turkey
Cihan Civan Civas - Department of Physiology, School of Medicine, Yeditepe University, Istanbul, Turkey
Muhammed Ikbal Alp - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Iltan Aklan - Department of Physiology, School of Medicine, Yeditepe University, Istanbul, Turkey
Edanur Ates Oz - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Yavuz Yavuz - Department of Physiology, School of Medicine, Yeditepe University, Istanbul, Turkey
Bayram Yilmaz - Department of Physiology, School of Medicine, Yeditepe University, Istanbul, Turkey
Nilufer Sayar Atasoy - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Deniz Atasoy - Department of Physiology, School of Medicine, Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey
Resource Type: Journal article
Publication Details: Neurobiology of disease, Vol.121, pp.58-64
DOI: 10.1016/j.nbd.2018.09.017
PMID: 30240706
NLM abbreviation: Neurobiol Dis
ISSN: 0969-9961
eISSN: 1095-953X
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100004410, name: Scientific and Technological Research Council of Turkey, award: 214S361
Language: English
Date published: 01/2019
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040225002771

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