Li Bin, Zhuang Qian-Xing, Gao He-Ren, Wang Jian-Jun, Zhu Jing-Ning
State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.
Brain Struct Funct. 2017 Mar;222(2):957-971. doi: 10.1007/s00429-016-1257-2. Epub 2016 Jun 24.
The cerebellum, a hindbrain motor center, also participates in regulating nonsomatic visceral activities such as feeding control. However, the underlying neural mechanism is largely unknown. Here, we investigate whether the cerebellar medial nucleus (MN), one of the final outputs of the cerebellum, could directly project to and modulate the feeding-related neurons in the ventromedial hypothalamic nucleus (VMN), which has been traditionally implicated in feeding behavior, energy balance, and body weight regulation. The retrograde tracing results show that both GABAergic and glutamatergic projection neurons in the cerebellar MN send direct projections to the VMN. Electrical stimulation of cerebellar MN elicits an inhibitory, excitatory or biphasic response of VMN neurons. Interestingly, the VMN neurons modulated by cerebellar MN afferents not only receive phasic and tonic inputs from the gastric vagal nerves, but also are sensitive to peripheral glycemia and ghrelin signals. Moreover, a summation of inputs from the cerebellar MN and gastric vagal afferents occurs on single glycemia/ghrelin-sensitive neurons in the VMN, and the immunostaining result show that the axons from the cerebellar MN and the projections from the nucleus tractus solitarius, which conveys the gastric vagal inputs to hypothalamus, converge on single VMN glycemia/ghrelin-sensitive neurons. These results demonstrate that the somatic information forwarded by the cerebellar MN, together with the feeding signals from periphery, converge onto single VMN neurons, suggesting that a somatic-visceral integration related to feeding may occur in the VMN and the cerebellum may actively participate in the feeding regulation through the direct cerebellar MN-VMN projections.
小脑作为后脑运动中枢,也参与调节非躯体内脏活动,如进食控制。然而,其潜在的神经机制在很大程度上尚不清楚。在此,我们研究小脑内侧核(MN)这一小脑的最终输出之一,是否能直接投射并调节腹内侧下丘脑核(VMN)中与进食相关的神经元,传统上认为该核与进食行为、能量平衡和体重调节有关。逆行示踪结果表明,小脑MN中的γ-氨基丁酸能和谷氨酸能投射神经元都直接投射到VMN。电刺激小脑MN会引发VMN神经元的抑制性、兴奋性或双相反应。有趣的是,受小脑MN传入纤维调节的VMN神经元不仅接受来自胃迷走神经的相位性和紧张性输入,还对外周血糖和胃饥饿素信号敏感。此外,小脑MN和胃迷走传入纤维的输入在VMN中单个血糖/胃饥饿素敏感神经元上发生总和,免疫染色结果表明,小脑MN的轴突和孤束核的投射(将胃迷走输入传递到下丘脑)汇聚在单个VMN血糖/胃饥饿素敏感神经元上。这些结果表明,小脑MN传递的躯体信息与来自外周的进食信号汇聚到单个VMN神经元上,提示在VMN中可能发生与进食相关的躯体-内脏整合,并且小脑可能通过直接的小脑MN-VMN投射积极参与进食调节。