Wiater MF, Mukherjee S, Dinh TT, Rooney E, Li A-J, Simasko SM, Ritter S (2010) The arcuate nucleus of the hypothalamus controls the circadian distribution of sleep and feeding. Neuroscience 2010 Abstracts 648.16/H17. Society for Neuroscience, San Diego, CA.
Summary: Integration of daily sleep and feeding rhythms is incompletely understood. We examined the role of the hypothalamic arcuate nucleus (Arc) in these processes using Arc microinjections of the targeted toxin, NPY-saporin (NPY-SAP), or control blank-saporin (B-SAP). NPY-sap targets and destroys NPY receptor-expressing neurons. We monitored 24 hr feeding over a 30-day period beginning 2 wks after the Arc injections, and used EEG recordings to assign vigilance states. Vigilance was divided into rapid-eye movement sleep (REMS), non-REMS (NREMS) and wake. NPY-SAP lesioned rats were hyperphagic , consuming up to 225% of pre-injection baseline. They rapidly became obese. While in the sleep-monitoring chambers, their body weight change per week ranged from 56 ± 9 g to 40.5 ± 4.5g, compared to 6 ± 0.4 g/wk for B-SAP rats. Their circadian pattern of food intake was severely disrupted, such that intake in light and dark periods were approximately equal (43% of their total intake was consumed in the light period vs. 25% in B-SAP controls). Sleep patterns were also significantly disrupted in the NPY-SAP animals. The occurrence of rapid eye movement sleep (REMS) was inverted in phase, occurring mainly at night, rather than during the day. NonREMS was distributed equally across day and night, instead of occurring predominantly during the day. However, 24-hr total REMS and NREMS time was normal. B-SAP controls had normal sleep patterns, with NREMS and REMS occurring predominantly in the light phase. To determine if the change in sleep pattern was due to the change in feeding patterns, we restricted access to food to the dark period for 4 days. NPY-SAP treated animals doubled their food intake in the dark period. However, sleep patterns were not changed compared to the ad libitum feeding period in either NPY-SAP or B-SAP rats. After 7 days of ad libitum feeding, we restricted food access to the light period for 4 days. Again, NPY-SAP animals doubled their intake during the feeding period, this time during the light phase, and sleep patterns were not changed in either group by the restricted feeding. By 100 days post-lesion, the NPY-sap animals were still obese, but the patterning and amount of their food intake were becoming similar to controls. However, when evaluated again, sleep patterns were still altered to the same degree as observed early post-lesion. These results confirm the importance of NPY-receptive Arc neurons in controlling food intake. They also reveal an unexpected role for the Arc in the timing of both NREMS and REMS that appears to be independent of the patterning of food intake.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)