The Dorsomedial Hypothalamic Nucleus Is Not Necessary for the Expression of Circadian Food-Anticipatory Activity in Rats

Restricted daytime feeding generates food-anticipatory activity (FAA) by entrainment of a circadian pacemaker separate from the light-entrainable pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been proposed as the site of food-entrainable oscillators critical for the expression of FAA, but another study found no effects of complete DMH ablation on FAA. To account for these different results, the authors examined methodological factors, including (1) cage configuration and feeding method and (2) use of social cues. Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle of the light period, using caging and feeding methods matching those of Gooley et al. (2006). Rats with partial or complete DMH ablation were less nocturnal during ad lib food access but exhibited normal FAA during restricted feeding, as quantified by FAA magnitude, ratios, latency to appearance, duration, and precision. To evaluate the use of social cues, intact rats naive to restricted-feeding schedules were food deprived for 72 h on 4 tests. Daytime activity increased during food deprivation, but the magnitude and waveform of this activity was not influenced by the presence of food-entrained rats exhibiting robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate meals by reacting to sounds from food-entrained intact rats in adjacent cabinets. These results confirm our previous finding that the DMH is not critical for normal expression of FAA in rats, and this observation is extended to food restriction methodologies used by other labs. The methodological differences that do underlie discrepant results remain unresolved, as does the location of food-entrainable oscillators, input pathways, and output pathways critical for FAA.

[1]  M. Yanagisawa,et al.  The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker , 2006, Proceedings of the National Academy of Sciences.

[2]  Takeshi Sakurai,et al.  Hypothalamic Orexin Neurons Regulate Arousal According to Energy Balance in Mice , 2003, Neuron.

[3]  T. Kilduff,et al.  Food- and light-entrained circadian rhythms in rats with hypocretin-2-saporin ablations of the lateral hypothalamus , 2003, Brain Research.

[4]  R. Mistlberger,et al.  Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[5]  S. Amir,et al.  The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[7]  J B Chambers,et al.  Cardiovascular responses to caloric restriction and thermoneutrality in C57BL/6J mice. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[8]  S. Amir,et al.  Restricted access to food, but not sucrose, saccharine, or salt, synchronizes the expression of Period2 protein in the limbic forebrain , 2007, Neuroscience.

[9]  F. Stephan,et al.  Feeding-entrained circadian rhythms in hypophysectomized rats with suprachiasmatic nucleus lesions. , 1999, The American journal of physiology.

[10]  Yoshiyuki Sakaki,et al.  Circadian Rhythms in Isolated Brain Regions , 2002, The Journal of Neuroscience.

[11]  F. Torrealba,et al.  Tuberomammillary nucleus activation anticipates feeding under a restricted schedule in rats , 2000, Neuroscience Letters.

[12]  L. Swanson,et al.  Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHAL in the rat , 1998, Brain Research Reviews.

[13]  S. Shibata,et al.  Restricted‐feeding‐induced anticipatory activity rhythm is associated with a phase‐shift of the expression of mPer1 and mPer2 mRNA in the cerebral cortex and hippocampus but not in the suprachiasmatic nucleus of mice , 2001, The European journal of neuroscience.

[14]  D. Zaretsky,et al.  Physiology and Pharmacology of Temperature Regulation The dorsomedial hypothalamus : a new player in thermoregulation , 2006 .

[15]  Ralph E. Mistlberger,et al.  Circadian food-anticipatory activity: Formal models and physiological mechanisms , 1994, Neuroscience & Biobehavioral Reviews.

[16]  T. Sakurai,et al.  Orexin Neurons Function in an Efferent Pathway of a Food-Entrainable Circadian Oscillator in Eliciting Food-Anticipatory Activity and Wakefulness , 2004, The Journal of Neuroscience.

[17]  E. Herzog,et al.  The Suprachiasmatic Nucleus Entrains, But Does Not Sustain, Circadian Rhythmicity in the Olfactory Bulb , 2004, The Journal of Neuroscience.

[18]  J. Ripperger,et al.  Lack of Food Anticipation in Per2 Mutant Mice , 2006, Current Biology.

[19]  F. Torrealba,et al.  Differential effects of infralimbic cortical lesions on temperature and locomotor activity responses to feeding in rats , 2005, Neuroscience.

[20]  F. Torrealba,et al.  Specific activation of histaminergic neurons during daily feeding anticipatory behavior in rats , 2005, Behavioural Brain Research.

[21]  F. Torrealba,et al.  Arousal and differential Fos expression in histaminergic neurons of the ascending arousal system during a feeding‐related motivated behaviour , 2005, The European journal of neuroscience.

[22]  C. Escobar,et al.  Restricted feeding schedules phase shift daily rhythms of c-Fos and protein Per1 immunoreactivity in corticolimbic regions in rats , 2007, Neuroscience.

[23]  B. Rusak,et al.  Food-Anticipatory Circadian Rhythms in Rats with Paraventricular and Lateral Hypothalamic Ablations , 1988 .

[24]  A. Davidson Search for the feeding-entrainable circadian oscillator: a complex proposition. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[25]  L W Swanson,et al.  Organization of projections from the dorsomedial nucleus of the hypothalamus: A PHA‐L study in the rat , 1996, The Journal of comparative neurology.

[26]  M. Menaker,et al.  Is the food‐entrainable circadian oscillator in the digestive system? , 2003, Genes, brain, and behavior.

[27]  David K. Welsh,et al.  Effect of running wheel availability on circadian patterns of sleep and wakefulness in mice , 1988, Physiology & Behavior.

[28]  R. Boakes,et al.  Activity-based anorexia: Ambient temperature has been a neglected factor , 2002, Psychonomic bulletin & review.

[29]  J. Herbert,et al.  The Suprachiasmatic Nucleus. The Mind's Clock. , 1994 .

[30]  Jun Lu,et al.  Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms , 2003, The Journal of Neuroscience.

[31]  Steven A. Brown,et al.  Peripheral Circadian Oscillators in Mammals: Time and Food , 2003, Journal of biological rhythms.

[32]  B. Rusak,et al.  Housing conditions influence the expression of food-anticipatory activity in mice , 2004, Physiology & Behavior.

[33]  F. Stephan,et al.  The “Other” Circadian System: Food as a Zeitgeber , 2002, Journal of biological rhythms.

[34]  S. Amir,et al.  Differential regulation of the expression of Period2 protein in the limbic forebrain and dorsomedial hypothalamus by daily limited access to highly palatable food in food-deprived and free-fed rats , 2007, Neuroscience.

[35]  J Gibbon,et al.  Daily Meal Anticipation: Interaction of Circadian and Interval Timing a , 1984, Annals of the New York Academy of Sciences.

[36]  S. McKnight,et al.  NPAS2: An Analog of Clock Operative in the Mammalian Forebrain , 2001, Science.

[37]  P. Sassone-Corsi,et al.  Environmental stimulus perception and control of circadian clocks , 2002, Current Opinion in Neurobiology.

[38]  Joshua J Gooley,et al.  The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms , 2006, Nature Neuroscience.

[39]  S. Shibata,et al.  Reduced food anticipatory activity in genetically orexin (hypocretin) neuron‐ablated mice , 2004, The European journal of neuroscience.

[40]  Z. Boulos,et al.  Food availability and daily biological rhythms , 1980, Neuroscience & Biobehavioral Reviews.