期刊
NEUROSCIENCE
卷 329, 期 -, 页码 66-73出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2016.04.054
关键词
estrogen-related receptor alpha; eating disorder; synaptic transmission; ventral striatum; miniature excitatory postsynaptic currents; sexual dimorphism
资金
- National Science Foundation Graduate Research Fellowship [2012140236-02]
- Brain and Behavior Foundation
- Klarman Family Foundation Grants Program in Eating Disorder Research
- American Heart Association Scientist Developmental Grant [14SDG20140054]
- University of Iowa Carver College of Medicine
- [MH-095972]
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge-ED, are mental illnesses characterized by high morbidity and mortality. While several studies have identified neural deficits in patients with EDs, the cellular and molecular basis of the underlying dysfunction has remained poorly understood. We previously identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) associated with development of EDs. Because ventral-striatal signaling is related to the reward and motivation circuitry thought to underlie EDs, we performed functional and structural analysis of ventral-striatal synapses in Esrra-null mice. Esrra-null female, but not male, mice exhibit altered miniature excitatory postsynaptic currents on medium spiny neurons (MSNs) in the ventral striatum, including increased frequency, increased amplitude, and decreased paired pulse ratio. These electrophysiological measures are associated with structural and molecular changes in synapses of MSNs in the ventral striatum, including fewer pre-synaptic glutamatergic vesicles and enhanced GluR1 function. Neuronal Esrra is thus required for maintaining normal synaptic function in the ventral striatum, which may offer mechanistic insights into the behavioral deficits observed in Esrra-null mice. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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