Department of Cell and Developmental Biology, Silberman Institute of Life Sciences 3-533, The Hebrew University of Jerusalem, 9190401, Jerusalem, Israel.
Center for Research on Pain, The Hebrew University of Jerusalem, 9190401, Jerusalem, Israel.
Exp Brain Res. 2021 Nov;239(11):3255-3266. doi: 10.1007/s00221-021-06204-7. Epub 2021 Aug 30.
The mesopontine tegmental anesthesia area (MPTA) was identified in rats as a singular brainstem locus at which microinjection of minute quantities of GABAergic agents rapidly and reversibly induces loss-of-consciousness and a state of general anesthesia, while lesioning renders animals insensitive to anesthetics at normal systemic doses. Obtaining similar results in mice has been challenging, however, slowing research progress on how anesthetics trigger brain-state transitions. We have identified roadblocks that impeded translation from rat to mouse and tentatively located the MPTA equivalent in this second species. We describe here a series of modifications to the rat protocol that allowed us to document pro-anesthetic changes in mice following localized stereotactic delivery of minute quantities (20 nL) of the GABA-receptor agonist muscimol into the brainstem mesopontine tegmentum. The optimal locus identified proved to be homologous to the MPTA in rats, and local neuronal populations in rats and mice were similar in size and shape. This outcome should facilitate application of the many innovative gene-based methodologies available primarily in mice to the study of how activity in brainstem MPTA neurons brings about anesthetic loss-of-consciousness and permits pain-free surgery.
中脑被盖腹侧麻醉区（MPTA）在大鼠中被确定为单一的脑干位置，在此位置微注射少量 GABA 能药物可迅速且可逆地诱导意识丧失和全身麻醉状态，而损伤则使动物对正常全身剂量的麻醉剂不敏感。然而，在小鼠中获得类似的结果具有挑战性，这减缓了关于麻醉剂如何引发脑状态转变的研究进展。我们已经确定了从大鼠到小鼠转化的障碍，并初步确定了这种第二种物种的 MPTA 等效物。我们在这里描述了对大鼠方案的一系列修改，这些修改使我们能够在局部立体定向将微量（20 nL）GABA 受体激动剂 muscimol 递送到脑干脑桥被盖腹侧后，记录到小鼠中的前麻醉变化。确定的最佳位置被证明与大鼠中的 MPTA 同源，并且大鼠和小鼠中的局部神经元群体在大小和形状上相似。这一结果应该有助于将主要在小鼠中使用的许多创新的基于基因的方法应用于研究脑干 MPTA 神经元的活动如何导致麻醉意识丧失，并允许进行无痛手术。
