Circadian rhythms of PERIOD1 expression in the dorsomedial hypothalamic nucleus in the absence of entrained food-anticipatory activity rhythms in rats

Previously, we investigated the role of neuropeptide Y and leptin-sensitive networks in the mediobasal hypothalamus in sleep and feeding and found profound homeostatic and circadian deficits with an intact suprachiasmatic nucleus. We propose that the arcuate nuclei (Arc) are required for the integration of homeostatic circadian systems, including temperature and activity. We tested this hypothesis using saporin toxin conjugated to leptin (Lep-SAP) injected into Arc in rats. Lep-SAP rats became obese and hyperphagic and progressed through a dynamic phase to a static phase of growth. Circadian rhythms were examined over 49 days during the static phase. Rats were maintained on a 12:12-h light-dark (LD) schedule for 13 days and, thereafter, maintained in continuous dark (DD). After the first 13 days of DD, food was restricted to 4 h/day for 10 days. We found that the activity of Lep-SAP rats was arrhythmic in DD, but that food anticipatory activity was, nevertheless, entrainable to the restricted feeding schedule, and the entrained rhythm persisted during the subsequent 3-day fast in DD. Thus, for activity, the circuitry for the light-entrainable oscillator, but not for the food-entrainable oscillator, was disabled by the Arc lesion. In contrast, temperature remained rhythmic in DD in the Lep-SAP rats and did not entrain to restricted feeding. We conclude that the leptin-sensitive network that includes the Arc is required for entrainment of activity by photic cues and entrainment of temperature by food, but is not required for entrainment of activity by food or temperature by photic cues.

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Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock

Scientific Reports ◽

10.1038/s41598-021-99266-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mario Caba ◽

Enrique Meza ◽

Carolina Escobar ◽

Angeles Jiménez ◽

Mario Daniel Caba-Flores ◽

...

Keyword(s):

Food Intake ◽

Hypothalamic Nucleus ◽

Restricted Feeding ◽

Adult Rats ◽

Peripheral Oscillators ◽

Food Anticipatory Activity ◽

Ad Libitum ◽

Anticipatory Activity ◽

Oxytocinergic Cells

AbstractThe mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

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Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

10.21203/rs.3.rs-622616/v1 ◽

2021 ◽

Author(s):

Mario Caba ◽

Enrique Meza ◽

Carolina Escobar ◽

Angeles Jiménez ◽

Mario Daniel Caba-Flores ◽

...

Keyword(s):

Food Intake ◽

Hypothalamic Nucleus ◽

Restricted Feeding ◽

Adult Rats ◽

Peripheral Oscillators ◽

Food Anticipatory Activity ◽

Ad Libitum ◽

Anticipatory Activity ◽

Oxytocinergic Cells

Abstract The mechanisms underlying food anticipatory activity is still not well understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON) and in the medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), Ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or Ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; contrasting, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

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The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2009.06697.x ◽

2009 ◽

Vol 29 (7) ◽

pp. 1447-1460 ◽

Cited By ~ 83

Author(s):

Takahiro Moriya ◽

Reiko Aida ◽

Takashi Kudo ◽

Masashi Akiyama ◽

Masao Doi ◽

...

Keyword(s):

Gene Expression ◽

Circadian Rhythms ◽

Clock Gene ◽

Hypothalamic Nucleus ◽

Clock Gene Expression ◽

Dorsomedial Hypothalamic Nucleus

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Food as circadian time cue for appetitive behavior

F1000Research ◽

10.12688/f1000research.20829.1 ◽

2020 ◽

Vol 9 ◽

pp. 61 ◽

Cited By ~ 2

Author(s):

Ralph E. Mistlberger

Keyword(s):

Ketone Bodies ◽

Dorsal Striatum ◽

Brain Regions ◽

Circadian Clocks ◽

Feeding Time ◽

Dopaminergic Drugs ◽

Activity Rhythms ◽

Circadian Oscillators ◽

Food Anticipatory Activity ◽

Anticipatory Activity

Feeding schedules entrain circadian clocks in multiple brain regions and most peripheral organs and tissues, thereby synchronizing daily rhythms of foraging behavior and physiology with times of day when food is most likely to be found. Entrainment of peripheral clocks to mealtime is accomplished by multiple feeding-related signals, including absorbed nutrients and metabolic hormones, acting in parallel or in series in a tissue-specific fashion. Less is known about the signals that synchronize circadian clocks in the brain with feeding time, some of which are presumed to generate the circadian rhythms of food-anticipatory activity that emerge when food is restricted to a fixed daily mealtime. In this commentary, I consider the possibility that food-anticipatory activity rhythms are driven or entrained by circulating ghrelin, ketone bodies or insulin. While evidence supports the potential of these signals to participate in the induction or amount of food-anticipatory behavior, it falls short of establishing either a necessary or sufficient role or accounting for circadian properties of anticipatory rhythms. The availability of multiple, circulating signals by which circadian oscillators in many brain regions might entrain to mealtime has supported a view that food-anticipatory rhythms of behavior are mediated by a broadly distributed system of clocks. The evidence, however, does not rule out the possibility that multiple peripheral and central food-entrained oscillators and feeding-related signals converge on circadian oscillators in a defined location which ultimately set the phase and gate the expression of anticipatory activity rhythms. A candidate location is the dorsal striatum, a core component of the neural system which mediates reward, motivation and action and which contains circadian oscillators entrainable by food and dopaminergic drugs. Systemic metabolic signals, such as ghrelin, ketones and insulin, may participate in circadian food anticipation to the extent that they modulate dopamine afferents to circadian clocks in this area.

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Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00023.2003 ◽

2003 ◽

Vol 285 (1) ◽

pp. R57-R67 ◽

Cited By ~ 74

Author(s):

SiNae Pitts ◽

Elizabeth Perone ◽

Rae Silver

Keyword(s):

Circadian Rhythms ◽

Clock Gene ◽

Wheel Running ◽

Mutant Mice ◽

Circadian Oscillators ◽

Daily Food ◽

Food Anticipatory Activity ◽

Anticipatory Activity ◽

The Brain ◽

Clock Protein

Daily scheduled feeding is a potent time cue that elicits anticipatory activity in rodents. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from light-entrained oscillators of the suprachiasmatic nucleus (SCN). Circadian rhythms within the SCN depend on transcription-translation feedback loops in which CLOCK protein is a key positive regulator. The Clock gene is expressed in rhythmic tissues throughout the brain and periphery, implicating its widespread involvement in the functioning of circadian oscillators. To examine whether CLOCK protein is also necessary for the FEO, the effect of daily food restriction was studied in homozygous Clock mutant ( Clk/Clk) mice. The results show that Clk/Clk mutant mice exhibit FAA, even when their circadian wheel-running behavior is arrhythmic. As in wild-type controls, FAA in Clk/Clk mutants persists after temporal feeding cues are removed for several cycles, indicating that the FEO is a circadian timer. This is the first demonstration that the Clock gene is not necessary for the expression of a circadian, food-entrained behavior and suggests that the FEO is mediated by a molecular mechanism distinct from that of the SCN.

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