The Endogenous Opioid Met-Enkephalin Modulates Thalamo-Cortical Excitation Inhibition Balance in a Medial Thalamus-Anterior Cingulate Cortex Circuit.
The Endogenous Opioid Met-Enkephalin Modulates Thalamo-Cortical Excitation Inhibition Balance in a Medial Thalamus-Anterior Cingulate Cortex Circuit.
复制标题
内源性阿片类脑啡肽调节内侧丘脑-前扣带皮层回路中的丘脑-皮质兴奋抑制平衡。
DOI：
10.1101/2023.07.13.547220
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Birdsong,William
中科院分区：
文献类型：
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作者：
Hervert,ErwinArias;Birdsong,William
前扣带回阿片受体的激活介导了外源性和内源性阿片类药物的镇痛作用。我们先前已经证明，阿片信号干扰了从内侧丘脑(MThal)到ACC的传入兴奋性和间接抑制性突触传递，但内源性阿片类药物在该回路中的作用仍然知之甚少。本研究的目的是了解内源性阿片类药物[Met]5-脑啡肽(ME)如何调节丘脑驱动的兴奋性和抑制性突触传递到ACC的V层锥体神经元。我们运用药理学、脑片电生理学和光基因刺激等方法，研究阿片类药物对光诱发谷氨酸和氨基丁酸能传递的调节作用。结果表明，ME抑制AMPA介导的兴奋性突触传递和GABA介导的抑制性突触传递。然而，ME对抑制性传递的抑制作用强于兴奋性传递。GABAA介导的突触传递的这种优先减少主要是由于ME激活了增量阿片受体，导致MThal-ACC兴奋通路的净解除抑制。这些结果提示，中等浓度的ME可引起ACC回路的净兴奋，其镇痛作用可能与去抑制有关，而不是与抑制ACC亚回路有关。
Activation of opioid receptors in the anterior cingulate cortex (ACC) mediates aspects of analgesia induced by both exogenous and endogenous opioids. We have previously shown that opioid signaling disrupts both afferent excitatory and indirect inhibitory synaptic transmission from the medial thalamus (MThal) to the ACC, but the effects of endogenous opioids within this circuit remain poorly understood. The goal of the current study was to understand how the endogenous opioid, [Met]5-enkephalin (ME), modulates thalamic-driven excitatory and inhibitory synaptic transmission onto layer V pyramidal neurons in the ACC. We used pharmacology, brain slice electrophysiology and optogenetic stimulation to study opioid-mediated modulation of optically evoked glutamatergic and GABAergic transmission. The results revealed that ME inhibited both AMPA-mediated excitatory and GABA-mediated inhibitory synaptic transmission in the ACC. However, inhibitory transmission was more potently inhibited than excitatory transmission by ME. This preferential reduction in GABAA-mediated synaptic transmission was primarily due to the activation of delta opioid receptors by ME and resulted in a net disinhibition of MThal-ACC excitatory pathway. These results suggest that moderate concentrations of ME can lead to net excitation of ACC circuitry and that analgesia may be associated with disinhibition rather than inhibition of ACC subcircuits.