Blaesse Peter, Goedecke Lena, Bazelot Michaël, Capogna Marco, Pape Hans-Christian, Jüngling Kay
Institute of Physiology I, University of Münster, D-48149 Münster, Germany.
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, OX1 3TH, United Kingdom, and GW Pharmaceuticals, School of Chemistry, Food and Nutritional Science and Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, United Kingdom.
J Neurosci. 2015 May 13;35(19):7317-25. doi: 10.1523/JNEUROSCI.0204-15.2015.
The amygdala is a key region for the processing of information underlying fear, anxiety, and fear extinction. Within the local neuronal networks of the amygdala, a population of inhibitory, intercalated neurons (ITCs) modulates the flow of information among various nuclei of amygdala, including the basal nucleus (BA) and the centromedial nucleus (CeM) of the amygdala. These ITCs have been shown to be important during fear extinction and are target of a variety of neurotransmitters and neuropeptides. Here we provide evidence that the activation of μ-opioid receptors (MORs) by the specific agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin) hyperpolarizes medially located ITCs (mITCs) in acute brain slices of mice. Moreover, we use whole-cell patch-clamp recordings in combination with local electrical stimulation or glutamate uncaging to analyze the effect of MOR activation on local microcircuits. We show that the GABAergic transmission between mITCs and CeM neurons is attenuated by DAMGO, whereas the glutamatergic transmission on CeM neurons and mITCs is unaffected. Furthermore, MOR activation induced by theta burst stimulation in BA suppresses plastic changes of feedforward inhibitory transmission onto CeM neurons as revealed by the MOR antagonist CTAP d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2. In summary, the mITCs constitute a target for the opioid system, and therefore, the activation of MOR in ITCs might play a central role in the modulation of the information processing between the basolateral complex of the amygdala and central nuclei of the amygdala.
杏仁核是处理恐惧、焦虑和恐惧消退相关信息的关键区域。在杏仁核的局部神经元网络中，一群抑制性的插入神经元（ITCs）调节着杏仁核各个核团之间的信息流，包括杏仁核的基底核（BA）和中央内侧核（CeM）。这些ITCs已被证明在恐惧消退过程中很重要，并且是多种神经递质和神经肽的作用靶点。在这里，我们提供证据表明，特异性激动剂DAMGO（[D-Ala2，N-Me-Phe4，Gly5-ol]-脑啡肽）激活μ-阿片受体（MORs）会使小鼠急性脑片中位于内侧的ITCs（mITCs）超极化。此外，我们结合局部电刺激或谷氨酸解笼技术，使用全细胞膜片钳记录来分析MOR激活对局部微电路的影响。我们发现，DAMGO会减弱mITCs和CeM神经元之间的GABA能传递，而对CeM神经元和mITCs上的谷氨酸能传递没有影响。此外，如MOR拮抗剂CTAP（d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2）所示，BA中θ爆发刺激诱导的MOR激活会抑制前馈抑制性传递到CeM神经元上的可塑性变化。总之，mITCs构成了阿片系统的一个作用靶点，因此，ITCs中MOR的激活可能在调节杏仁核基底外侧复合体和杏仁核中央核之间的信息处理中起核心作用。
