title: Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.
abstract: Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABAAR) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABAAR to amygdala inhibition and fear.
  
  
  
  By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABAAR (GABAA(δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABAA(δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior.
  
  
  
  In sharp contrast to the established role of synaptic GABAAR in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABAA(δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABAA(δ)R. The disinhibition arose from IN-specific expression of GABAA(δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABAA(δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABAA(δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear.
  
  
  
  Our findings suggest that GABAA(δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABAA(δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion.
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Zhi-Peng
authors: ZP
authors: Liu
authors: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province; Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou.
authors: Qing-Hai
authors: QH
authors: He
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Han-Qing
authors: HQ
authors: Pan
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Xiao-Bin
authors: XB
authors: Xu
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Wen-Bing
authors: WB
authors: Chen
authors: Medical Experiment Center, Nanchang University, Nanchang.
authors: Ye
authors: Y
authors: He
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Jin
authors: J
authors: Zhou
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Wen-Hua
authors: WH
authors: Zhang
authors: Department of Biotechnology, School of Life Sciences, Nanchang University, Nanchang.
authors: Jun-Yu
authors: JY
authors: Zhang
authors: Department of Neurology, the 2nd Affiliated Hospital, , Nanchang University, Nanchang.
authors: Xiao-Ping
authors: XP
authors: Ying
authors: Institute of Translational Medicine, Nanchang University, Nanchang.
authors: Ren-Wen
authors: RW
authors: Han
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang.
authors: Bao-Ming
authors: BM
authors: Li
authors: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province; Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou.
authors: Tian-Ming
authors: TM
authors: Gao
authors: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang; Department of Neurology, the 2nd Affiliated Hospital, , Nanchang University, Nanchang; Jiangxi Provincial Collaborative Innovation Center for Cardiovascular, Digestive and Neuropsychiatric Diseases, Jiangxi, China. Electronic address: panbingxing@ncu.edu.cn.
authors: Bing-Xing
authors: BX
authors: Pan
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005239:Fear / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A
keywords: Disinhibition; Fear; GABA; Interneuron; LTP; Lateral amygdala