Pharmacology Institute, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany.
Nat Commun. 2022 Aug 25;13(1):5014. doi: 10.1038/s41467-022-32558-9.
The basal nucleus of Meynert (NBM) subserves critically important functions in attention, arousal and cognition via its profound modulation of neocortical activity and is emerging as a key target in Alzheimer's and Parkinson's dementias. Despite the crucial role of neocortical domains in pain perception, however, the NBM has not been studied in models of chronic pain. Here, using in vivo tetrode recordings in behaving mice, we report that beta and gamma oscillatory activity is evoked in the NBM by noxious stimuli and is facilitated at peak inflammatory pain-like behavior. Optogenetic and chemogenetic cell-specific, reversible manipulations of NBM cholinergic-GABAergic neurons reveal their role in endogenous control of nociceptive hypersensitivity, which are manifest via projections to the prelimbic cortex, resulting in layer 5-mediated antinociception. Our data unravel the importance of the NBM in top-down control of neocortical processing of pain-like behavior.
梅尼埃基底核（NBM）通过对新皮层活动的深刻调节，在注意力、觉醒和认知方面发挥着至关重要的作用，并且正在成为阿尔茨海默病和帕金森病痴呆症的关键靶点。然而，尽管新皮层在疼痛感知中具有至关重要的作用，但 NBM 在慢性疼痛模型中尚未得到研究。在这里，我们使用行为小鼠的体内四极管记录，报告说有害刺激会在 NBM 中引发β和γ振荡活动，并在炎症性疼痛样行为的高峰期得到促进。NBM 胆碱能-γ-氨基丁酸能神经元的光遗传学和化学遗传学细胞特异性、可逆操纵揭示了它们在伤害感受性过敏的内源性控制中的作用，这是通过投射到前扣带皮层来实现的，从而导致 5 层介导的镇痛。我们的数据揭示了 NBM 在自上而下控制疼痛样行为的新皮层处理中的重要性。
