Research ReportThe dynamics of neuronal activation during food anticipation and feeding in the brain of food-entrained rats
Introduction
The appropriate feeding behavior is essential for the survival of animals. This behavior should be coordinated with environmental conditions, such as the light–dark cycle and food availability, and internal physiological requirements, such as maintaining gastrointestinal functions and energy balance. The suprachiasmatic nucleus (SCN), which is regarded as the light-entrainable oscillator (LEO), orchestrates multiple circadian rhythms in the organism that are regulated according to environmental light/dark signals conveyed by the retinohypothalamic tract directly to the SCN (Hastings et al., 2003, Lowrey and Takahashi, 2004). However, when food availability is restricted to a few hours scheduled at a fixed time of the day, animals develop food-entrained circadian rhythms. Rats maintained on restricted feeding schedules (RFS) exhibit the behavior called food-anticipatory activity (FAA) that is manifested within the hours preceding food access by arousal and increased exploration and foraging locomotion (Stephan, 2001). Core temperature, plasma corticosterone, and free fatty acids shift their phase in anticipation of a daily meal (Diaz-Munoz et al., 2000, Escobar et al., 1998, Krieger, 1979). Biological rhythms associated with RFS persist after complete bilateral lesions of the SCN (Marchant and Mistlberger, 1997, Mistlberger, 1993), indicating the presence of a food-entrainable oscillator (FEO) that may function independently of the SCN.
Although much effort has been invested in the elucidation of a FEO, the possible elements of this oscillator are not yet fully understood. The persistence of FAA after adrenalectomy (Boulos and Terman, 1980), subdiaphragmatic vagotomy (Comperatore and Stephan, 1990, Moreira and Krieger, 1982), and capsaicin-induced deafferentiation (Davidson and Stephan, 1998) argues against the peripheral location of the FEO. Moreover, the importance of the liver or the pancreas as a possible component of the FEO was disproved in studies involving cirrhotic (Escobar et al., 2002) and diabetic (Davidson et al., 2002) rats.
In an attempt to locate the FEO in the central nervous system, several groups have produced ablations of potential anatomic substrates of this oscillator in the brain and explored its effects on the expression of FAA. In food-entrained rats, bilateral lesions of the ventromedial hypothalamic nucleus (VMH) did not prevent FAA or the preceding corticosterone peak (Honma et al., 1987, Mistlberger and Rechtschaffen, 1984). Likewise, bilateral lesions of the lateral hypothalamic area (LHA) and the paraventricular hypothalamic nucleus (PVH) failed to abolish FAA (Mistlberger and Rusak, 1988), and similar negative results were obtained after the lesion of the olfactory bulb (Davidson et al., 2001b), components of the limbic system (Mistlberger and Mumby, 1992), and the area postrema (Davidson et al., 2001a). Recent claims that the dorsomedial hypothalamic nucleus (DMH) is critical for the development of FAA (Gooley et al., 2006) appear to be controversial, as other groups working with rats (Landry et al., 2006) and mice (Moriya et al., 2007) have been unable to confirm that DMH ablation eliminates food-anticipatory behavior.
Because the identification of a single structure as a substrate of FEO has not been successful, it has been suggested that the FEO may be represented by a distributed and possibly redundant neuronal network interacting with peripheral systems related to digestion and energy metabolism (Escobar et al., 1998, Stephan, 2001). This inference is supported by a significant attenuation of the expression of FAA after genetic ablation of the clock-related Per2 gene (Feillet et al., 2006) that is expressed in a number of brain structures, including the cortex, limbic system, thalamus, and hypothalamus (Shieh, 2003).
In the brain of rats subjected to RFS, the expression of the Fos protein, the marker of neuronal activation, was detected as early as 2 h before the expected meal in some limbic structures such as the lateral septum and nucleus accumbens, and in the DMH, LHA, and paraventricular thalamic nucleus (PVT) at the time of expected feeding (Angeles-Castellanos et al., 2004, Angeles-Castellanos et al., 2007, Johnstone et al., 2006, Mendoza et al., 2005, Nakahara et al., 2004). Expression of c-fos mRNA, which precedes synthesis of the Fos protein, has not been detected before in the brain of food-anticipating rats.
The present study investigated the dynamics of neuronal activation in the rat brain during food anticipation at 3, 2, and 1 h before the expected meal, at the time of usual access to food and following 1 h of feeding. This experimental design was aimed to reveal which brain structures were activated and how this activation spread during food anticipation, and compare the neuronal activation during food anticipation and feeding. We hypothesized that the key structures triggering central activation and behavioral response would activate early during the period of anticipation and that the pattern of neuronal activation during food anticipation would not be similar to that described for feeding (Timofeeva et al., 2002).
It is known that behavioral activation during food anticipation coincides with an increase in the plasma levels of corticosterone. On the other hand, there is no evidence that the levels of corticotropin releasing factor (CRF) transcript in the parvocellular part of the PVH or serum ACTH are altered during FAA (Belda et al., 2005, Pesonen et al., 1992). Our previous studies have demonstrated that an increase in plasma corticosterone during acute fasting was not accompanied by neuronal activation of the PVH neurons or by an increase in PVH CRF expression (Timofeeva and Richard, 1997, Timofeeva and Richard, 2001, Timofeeva et al., 2002). The increase in fasting plasma corticosterone was attributed to a reduction in the plasma clearance rate of this hormone (Kiss et al., 1994, Woodward et al., 1991) aimed to mobilize the energy resources in this catabolic state (Richard et al., 2000). In the present study, we aimed to clarify whether the increase in plasma corticosterone in food-anticipating rats coincides with an increase in the expression of c-fos or CRF mRNAs in the PVH.
The results have revealed that in the brain of rats subjected to RFS, the septohippocampal, paraventricular thalamic, and dorsomedial hypothalamic nuclei were activated as early as 3 h before the expected meal. These brain regions may represent the food-entrainable brain oscillator and may trigger further central activation and behavioral food-anticipatory reaction. The pattern of neuronal activation during food anticipation was different from that induced by feeding for some specific brain regions or some subnuclei of the areas sensitive to both food anticipation and feeding conditions. Finally, the present data represent evidence that the anticipating increase in plasma corticosterone is not accompanied by an enhancement in c-fos and CRF PVH expression and suggest that factors other than CRF are involved in the control of adrenocortical secretion under RFS.
Section snippets
Food intake and body weight
Ad libitum (AL) fed rats consumed 20.87 ± 1.92 g of food over a 24-hour period. Food-restricted rats, whose access to food was limited to 2 h per day (Fig. 1, panel A), progressively adapted to the RFS and increased quantity of consumed food. Thus, on the first day of scheduled feeding, food-restricted rats ate only 38.70% (8.08 ± 2.33 g) of the AL daily intake. During the second week of scheduled feeding, food-restricted rats consumed 69.59% (14.53 ± 2.14 g) of the AL daily intake during 2 h of
Discussion
The present study was designed to detect the dynamics of neuronal activation in the rat brain during food anticipation and following feeding. This experimental design was aimed to reveal which brain structures were activated early and how this activation spread during the period of anticipation. The hypothesis proposed that the key structures triggering central activation and behavioral response would activate early during the period of anticipation and that the pattern of neuronal activation
Animals and housing conditions
Male Wistar rats, aged 6 weeks, were purchased from the Canadian Breeding Laboratories (St-Constant, QC, Canada). Animals were housed individually in wire-bottom cages suspended above absorbent paper and were maintained on a 12:12 h dark–light cycle (lights on between 06h00 and 18h00), with ambient temperature of 23 ± 1 °C, free access to tap water, and regular laboratory rat diet (Agway Prolab, Rat/Mouse/Hamster 1000 Formula), unless otherwise specified. Rats were acclimated to environmental
Acknowledgments
This work was supported by grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). E.T. is a scholar of Fonds de la Recherche en Santé du Québec (FRSQ). We thank Julie Plamondon for her technical assistance.
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2018, Brain ResearchCitation Excerpt :This ability to anticipate scheduled meals is referred to as food entrainable oscillation (FEO). FEO is associated with activation of the hippocampus (Hp), medial prefrontal cortex (mPFC), nucleus accumbens (NAc), ventral tegmental area (VTA), arcuate (Arc), and dorsomedial (DMH) nucleus of the hypothalamus (Poulin and Timofeeva, 2008). Numerous lesions studies have failed to determine one single brain region in this network that reduces FEO suggesting that this behavior is controlled by distributed activity within this network.