Extrasynaptic GABAA Receptors in Mediodorsal Thalamic Nucleus Modulate Fear Extinction Learning

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Title
Extrasynaptic GABAA Receptors in Mediodorsal Thalamic Nucleus Modulate Fear Extinction Learning
Author(s)
Afshin Paydar; Bo Yong Lee; Gireesh Gangadharan; Sukchan Lee; Eun Mi Hwang; Hee Sup Shin
Publication Date
2014-05
Journal
MOLECULAR BRAIN, v.7, no.1, pp.39 -
Publisher
BIOMED CENTRAL LTD
Abstract
Background: The gamma-amino-butyric acid (GABA) system is a critical mediator of fear extinction process. GABA can induce “phasic” or “tonic” inhibition in neurons through synaptic or extrasynaptic GABAA receptors, respectively. However, role of the thalamic “tonic GABA inhibition” in cognition has not been explored. We addressed this issue in extinction of conditioned fear in mice. Results: Here, we show that GABAA receptors in the mediodorsal thalamic nucleus (MD) modulate fear extinction. Microinjection of gabazine, a GABAA receptor antagonist, into the MD decreased freezing behavior in response to the conditioned stimulus and thus facilitated fear extinction. Interestingly, microinjection of THIP (4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol), a preferential agonist for the δ-subunit of extrasynaptic GABAA receptors, into the MD attenuated fear extinction. In the opposite direction, an MD-specific knock-out of the extrasynaptic GABAA receptors facilitated fear extinction. Conclusions: Our results suggest that “tonic GABA inhibition” mediated by extrasynaptic GABAA receptors in MD neurons, suppresses fear extinction learning. These results raise a possibility that pharmacological control of tonic mode of GABAA receptor activation may be a target for treatment of anxiety disorders like post-traumatic stress disorder.
URI
https://pr.ibs.re.kr/handle/8788114/1515
ISSN
1756-6606
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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