Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator?

Several endogenous oscillators determine circadian rhythms. One, light-entrained, is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and feeding affect rhythms, we compared nocturnally active rats fed either ad libitum or for 2 hr/d during light [restricted feeding (RF)] and either with or without colchicine-induced disruption of VMN. We measured rhythms in temperature, locomotor activity, feeding, drinking, corticosterone, and the numbers of cells expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN, whereas the VMN and sPVNz lacked light/dark differences except after RF and RF plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere maintaining dark > light. By contrast, levels of corticosterone peaked before food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos activity driven by the SCN. The VMN may contain a food-entrained oscillator, and the sPVNz may integrate output from several oscillators.