title: Loss of estrogen-related receptor alpha disrupts ventral-striatal synaptic function in female mice.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Héctor
authors.initials: H
authors.lastname: De Jesús-Cortés
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Psychology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Anderson
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Khan
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Nath
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Latisha
authors.initials: L
authors.lastname: McDaniel
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lutter
authors.affiliation: Department of Psychology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Radley
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA; Department of Neurology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA; Free Radical & Radiation Biology Program, Department of Radiation Oncology Holden Comprehensive Cancer Center, University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pieper
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, USA. Electronic address: Huxing-Cui@uiowa.edu.
authors.forename: Huxing
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000172:deficiency* / Q000235:genetics; D012727:Sex Characteristics; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D018698:Glutamic Acid; D018091:Receptors, AMPA; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor
keywords: eating disorder; estrogen-related receptor alpha; miniature excitatory postsynaptic currents; sexual dimorphism; synaptic transmission; ventral striatum