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Behav Brain Res. 2016 Oct 15;313:135-43. doi: 10.1016/j.bbr.2016.07.002. Epub 2016 Jul 4.

The essential role of hippocampal alpha6 subunit-containing GABAA receptors in maternal separation stress-induced adolescent depressive behaviors.

Author information

1
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.
2
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.
3
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62966, United States.
4
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.
5
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.

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.

KEYWORDS:

Depression; GABAA receptor; Hippocampus; Maternal separation stress; Synaptic transmission

PMID:
27388150
DOI:
10.1016/j.bbr.2016.07.002
[Indexed for MEDLINE]

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