The cerebellum harbors a circadian oscillator involved in food anticipation.
The cerebellum participates in motor coordination as well as in numerous cerebral processes, including temporal discrimination. Animals can predict daily timing of food availability, as manifested by food-anticipatory activity under restricted feeding. By studying ex vivo clock gene expression by in situ hybridization and recording in vitro Per1-luciferase bioluminescence, we report that the cerebellum contains a circadian oscillator sensitive to feeding cues (i.e., whose clock gene oscillations are shifted in response to restricted feeding). Food-anticipatory activity was markedly reduced in mice injected intracerebroventricularly with an immunotoxin that depletes Purkinje cells (i.e., OX7-saporin). Mice bearing the hotfoot mutation (i.e., Grid2(ho/ho)) have impaired cerebellar circuitry and mild ataxic phenotype. Grid2(ho/ho) mice fed ad libitum showed regular behavioral rhythms and day-night variations of clock gene expression in the hypothalamus and cerebellum. When challenged with restricted feeding, however, Grid2(ho/ho) mice did not show any food-anticipatory rhythms, nor timed feeding-induced changes in cerebellar clock gene expression. In hypothalamic arcuate and dorsomedial nuclei, however, shifts in Per1 expression in response to restricted feeding were similar in cerebellar mutant and wild-type mice. Furthermore, plasma corticosterone and metabolites before mealtime did not differ between cerebellar mutant and wild-type mice. Together, these data define a role for the cerebellum in the circadian timing network and indicate that the cerebellar oscillator is required for anticipation of mealtime.
Département de Neurobiologie des Rythmes, Centre National de la Recherche Scientifique, Unité Propre de Recherche 3212 associée à l'Université de Strasbourg, Institut Fédératif des Neurosciences de Strasbourg, 67084 Strasbourg, France.
Jorge
J
Mendoza
Paul
P
Pévet
Marie-Paule
MP
Felder-Schmittbuhl
Yannick
Y
Bailly
Etienne
E
Challet
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D056926:CLOCK Proteins / Q000378:metabolism; D002531:Cerebellum / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics*; D005247:Feeding Behavior / Q000502:physiology; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism; D056950:Period Circadian Proteins / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic
C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D008156:Luciferases; D056926:CLOCK Proteins; C538944:Clock protein, mouse