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

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.