Cerebellar Fastigial Nuclear Inputs and Peripheral Feeding Signals Converge on Neurons in the Dorsomedial Hypothalamic Nucleus

Abstract

Previous studies have indicated that neurons in the dorsomedial hypothalamic nucleus (DMN) receive feeding-related signals from the gastric vagal nerves, glycemia as well as leptin. On the other hand, it is intriguing that the cerebellum participates in regulating nonsomatic visceral activities including food intake via the direct cerebellohypothalamic projections. The present study was designed to examine, by using extracellular recordings in vivo in rats, whether the cerebellar fastigial nucleus (FN) could reach and converge with the feeding-associated gastric vagal, glycemia and leptin signals onto single DMN neurons. Of the 200 DMN neurons recorded, 104 (52%) responded to the cerebellar FN stimulation, in which 95 (91.3%) were also responsive to the gastric vagal stimulation, suggesting a convergence of cerebellar FN and gastric vagal inputs on the DMN neurons. Moreover, a summation of responses was observed (n = 10) when the cerebellar FN and gastric vagal nerve were simultaneously stimulated. Among the 18 DMN neurons receiving convergent inputs from the cerebellar FN and gastric vagal nerves, 16 (88.9%) cells also responded to the systemic administrations of glucose and leptin. These results demonstrated that the cerebellar FN-afferent inputs, together with the feeding signals from the gastric vagal nerves, blood glucose as well as leptin, converge onto single DMN neurons, suggesting that a somatic-visceral integration related to the feeding may occur in the DMN and the cerebellum may actively participate in the feeding regulation through the cerebellar FN-DMN projections.

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

“…Because changes of Per1 expression in the arcuate and dorsomedial hypothalamic nuclei were similar in food-restricted wild-type mice and Grid2 ho/ho mice, respectively, expressing or not food-anticipatory activity, this finding suggests that the mediobasal hypothalamus is not critical for cerebellar synchronization to feeding. In addition another route exists, identified by extracellular recording in the deep cerebellar nuclei after gastric vagal stimulation, which conveys peripheral signals to the cerebellar network via the vagus nerve (Li et al, 2009). These data indicate that the cerebellum can either directly sense metabolic signals or receive them indirectly via multiple neural projections.…”

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

“…Previous studies from our laboratory have demonstrated that the cerebellar MN and/or interpositus nucleus widely modulated the neuronal activities of several hypothalamic nucleus/areas, including the LHA, VMN, dorsomedial hypothalamic nucleus (DMN) and paraventricular nucleus of the hypothalamus (Pu et al 1995;Wang et al 1997;Zhang et al 2003Zhang et al , 2005Zhu et al 2004Zhu et al , 2006aWen et al 2004;Li et al 2009). Interestingly, neurons in these hypothalamic nucleus/areas responded to the cerebellar MN and interpositus nucleus in a quite similar manner, and most of them were closely associated with feeding control, suggesting that the cerebellum may participate in feeding regulation by parallel modulation on multiple hypothalamic centers.…”

“…Brief double-negative rectangular pulses were applied to stimulate the cerebellar MN (intensity 50-200 lA, duration 0.4 ms, interval 10 ms) (Zhang et al 2003;Min et al 1989;Katafuchi and Koizumi 1990;Li et al 2009;Zhu et al 2006a) and gastric vagal nerves (intensity 300-500 lA, duration 0.5 ms, interval 10 ms) Barber 1992, 1996;Li et al 2009;Zhu et al 2007). The paired pulses were given to the cerebellar MN or/and gastric vagal nerves every 15 s up to 100 trials for constructing a peristimulus time histogram (PSTH, see below for details).…”

“…The response patterns of VMN neurons were determined by comparing the discharge rate before and after the stimulation/administration. According to the previous established criteria (Min et al 1989;Zhang et al 2003Zhang et al , 2005Wen et al 2004;Zhu et al 2004Zhu et al , 2006aLi et al 2009), inhibition from stimulation was significant if the discharge frequency decreased at least to 30 % (70 % change) of the basal rate, and excitation was significant if the discharge frequency increased to at least 200 % (100 % change) of the basal firing level. Furthermore, statistical analyses were performed using Student's t test.…”

Low levels of citrin (SLC25A13) expression in adult mouse brain restricted to neuronal clusters

“…Nonetheless, the cerebellar deep nuclei, where citrin is expressed most, appear to have a role in the regulation of nonsomatic activities, particularly visceral activities, associated with feeding behavior (Zhu and Wang, 2008). There are neural pathways that connect directly the deep cerebellar nuclei and hypothalamic nuclei involved in feeding control, and these cerebellohypothalamic projections form a bridge through which the cerebellum may participate in the regulation of food intake (Zhu et al, 2004;Zhu and Wang, 2008;Li et al, 2009). Determining whether citrin up-regulation is related to enhanced glucose or lactate utilization in specific neurons involved in feeding control or is merely a residual response to the same cues 9.56 6 1.5* (202) 6.1 6 0.84 (129) Liver 22.2 6 1.9 37.36 3.3** (168) 29.8 6 4 (134) y b-Galactosidase activity was measured as stated in Materials and Methods in cytosolic fractions of cortex, cerebellum (n 5 5), and liver (n 5 3) in citrin-deficient mice fed ad libitum (control), or 24-hr fasted, or 24-hr fasted plus 48-hr refed.…”