title: The essential role of hippocampal alpha6 subunit-containing GABAA receptors in maternal separation stress-induced adolescent depressive behaviors.
abstract: Exposure to early stressful adverse life events such as maternal separation severely impacts the development of the nervous system. Using immunohistochemistry, quantitative PCR and Western blot approaches, we found that alpha6 subunit-containing GABAA receptors (Gabra6-containing GABAA Rs) were expressed on hippocampal interneurons of adolescent rats. Maternal separation stress (MS) from postnatal day 2 to15 significantly reduced Gabra6 expression and provoked depressive behaviors such as anhedonia. Furosemide, the selective antagonist of Gabra6-containing GABAARs, strongly increased peak amplitude of evoked IPSCs at CA3-CA1 synapses and the frequency of miniature IPSPs recorded from CA1 pyramidal cells in naive control animals, and this effect was occluded in MS animals. Knockdown of Gabra6 expression in hippocampus mimicked furosemide's effect and was sufficient to produce similar depressive symptoms that were observed in MS animals. These results indicate that the Gabra6-containing GABAA R is a key modulator of hippocampal synaptic transmission and likely plays a crucial role in the pathophysiology of maternal separation-induced depression.
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Yang
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China; Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62966, United States.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62966, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Wei
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Li
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China.
authors.forename: Mingfa
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL 62966, United States; Center for Integrated Research in Cognitive & Neural Sciences, Carbondale, IL 62966, United States.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rose
authors.affiliation: The Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated hospital of Guangzhou Medical University, Guangzhou 510030, PR China; Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62966, United States; Center for Integrated Research in Cognitive & Neural Sciences, Carbondale, IL 62966, United States. Electronic address: cai001@siu.edu.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cai
mesh_terms: D059445:Anhedonia; D000818:Animals; D003863:Depression / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000378:metabolism; D008426:Maternal Deprivation; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D058787:GABA-A Receptor Antagonists; C546173:Gabra6 protein, rat; D011963:Receptors, GABA-A; D005665:Furosemide
keywords: Depression; GABAA receptor; Hippocampus; Maternal separation stress; Synaptic transmission