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Medial cerebellar nucleus projects to feeding-related neurons in the ventromedial hypothalamic nucleus in rats

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Abstract

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant numbers 31330033, 91332124, 31471112, 31500848, and NSFC/RGC Joint Research Scheme 31461163001); the State Educational Ministry of China (SRFDP/RGC ERG Grant 20130091140003, and Fundamental Research Funds for the Central Universities 020814380004 and 20620140565); the Natural Science Foundation of Jiangsu Province, China (Grant numbers BK2011014, BK20140599 and BK20151384); and the China Postdoctoral Sciences Foundation (Grant numbers 2011M500089, 2013T60520).

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    1. 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

      Bin Li, Qian-Xing Zhuang, He-Ren Gao, Jian-Jun Wang & Jing-Ning Zhu

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    1. Bin Li
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    Correspondence to Jian-Jun Wang or Jing-Ning Zhu.

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    B. Li and Q.-X. Zhuang contributed equally.

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    Li, B., Zhuang, QX., Gao, HR. et al. Medial cerebellar nucleus projects to feeding-related neurons in the ventromedial hypothalamic nucleus in rats. Brain Struct Funct 222, 957–971 (2017). https://doi.org/10.1007/s00429-016-1257-2

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