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首页> 外文期刊>Molecular brain >Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear extinction learning
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Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear extinction learning

机译：舌内侧丘脑核中突触外GABA A 受体调节恐惧消灭学习

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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.
机译：背景γ-氨基丁酸（GABA）系统是恐惧消灭过程的关键媒介。 GABA可以分别通过突触或突触外GABAA受体诱导神经元的“阶段性”或“紧张性”抑制。但是，尚未探索丘脑“强直GABA抑制”在认知中的作用。我们通过消除小鼠的条件性恐惧来解决这个问题。结果在这里，我们显示了中腹丘脑核（MD）中的GABAA受体调节了恐惧的消失。在条件刺激下向医学博士中微注射一种GABAA受体拮抗剂gabazine降低了冰冻行为，从而促进了恐惧的消除。有趣的是，将THIP（4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇）作为突触外GABAA受体δ亚基的优先激动剂显微注射至MD，从而减轻了恐惧的消失。在相反的方向上，突触外GABAA受体的MD特异性敲除促进了恐惧的消失。结论我们的研究结果表明，MD神经元中突触外GABAA受体介导的“强直GABA抑制”抑制恐惧消灭学习。这些结果提出了一种可能性，即药理控制GABAA受体激活的强直模式可能成为治疗诸如创伤后应激障碍等焦虑症的靶标。

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