Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb.
Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb.
复制标题
大麻素受体介导的对主嗅球二尖瓣细胞的抑制性输入的调节。
DOI：
10.1152/jn.00100.2018
复制
发表时间：
2019
影响因子：
2.5
通讯作者：
Heinbockel,Thomas
中科院分区：
文献类型：
--
作者：
Wang,Ze-Jun;Hu,SherryShu-Jung;Bradshaw,HeatherB;Sun,Liqin;Mackie,Ken;Straiker,Alex;Heinbockel,Thomas
内源性大麻素（eCB）信号系统在许多脑区都有功能上的影响。我们对大麻素受体1型（CB1）在嗅觉加工中的作用的理解仍然有限。大麻素信号参与调节主嗅球（MOB）的肾小球活动。然而，大麻素相关的电路输入到二尖瓣细胞在MOB尚未完全确定。利用解剖学和功能性方法，我们探讨了这个问题。cb1存在于gad65阳性中间神经元亚群的肾小球周围突起中，但不存在于二尖瓣细胞中。我们检测了小鼠MOB中的eCBs，以及MOB中cb1和其他与大麻素信号相关的基因的表达。膜片钳电生理学证明cb1激动剂激活二尖瓣细胞并引起向内电流，而cb1拮抗剂减少放电并引起向外电流。去除嗅神经层和肾小球层的肾小球下切片未见cb1对二尖瓣细胞的影响，提示肾小球层是cb1的作用部位。我们之前观察到，与二尖瓣细胞相比，gabaergy肾小球周围细胞对cb1的激活表现出相反的反应模式，这表明cb1通过肾小球gabaergy过程的细胞激活间接调节二尖瓣细胞的活性。大麻素调节突触传递到二尖瓣细胞的发现支持了这一假设。我们得出结论，cb1直接调节肾小球层的GABA能过程来控制GABA的释放，进而调节二尖瓣细胞的活性，对嗅觉阈值和行为有潜在的影响。大麻素信号与大麻素受体1型（CB1）参与主嗅球（MOB）肾小球活动的调节。我们在小鼠MOB中检测内源性大麻素。cb1存在于gad65阳性中间神经元亚群的肾小球周围突起中。cb1激动剂激活二尖瓣细胞。cb1直接调节GABA能过程，控制GABA释放，进而调节二尖瓣细胞活性，对嗅觉阈值和行为有潜在影响。
The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions. Our understanding of the role of cannabinoid receptor type 1 (CB1) in olfactory processing remains limited. Cannabinoid signaling is involved in regulating glomerular activity in the main olfactory bulb (MOB). However, the cannabinoid-related circuitry of inputs to mitral cells in the MOB has not been fully determined. Using anatomical and functional approaches we have explored this question. CB1was present in periglomerular processes of a GAD65-positive subpopulation of interneurons but not in mitral cells. We detected eCBs in the mouse MOB as well as the expression of CB1and other genes associated with cannabinoid signaling in the MOB. Patch-clamp electrophysiology demonstrated that CB1agonists activated mitral cells and evoked an inward current, while CB1antagonists reduced firing and evoked an outward current. CB1effects on mitral cells were absent in subglomerular slices in which the olfactory nerve layer and glomerular layer were removed, suggesting the glomerular layer as the site of CB1action. We previously observed that GABAergic periglomerular cells show the inverse response pattern to CB1activation compared with mitral cells, suggesting that CB1indirectly regulates mitral cell activity as a result of cellular activation of glomerular GABAergic processes . This hypothesis was supported by the finding that cannabinoids modulated synaptic transmission to mitral cells. We conclude that CB1directly regulates GABAergic processes in the glomerular layer to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.NEW & NOTEWORTHYCannabinoid signaling with cannabinoid receptor type 1 (CB1) is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). We detected endocannabinoids in the mouse MOB. CB1was present in periglomerular processes of a GAD65-positive subpopulation of interneurons. CB1agonists activated mitral cells. CB1directly regulates GABAergic processes to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.