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Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice.

Gallardo CM, Darvas M, Oviatt M, Chang CH, Michalik M, Huddy TF, Meyer EE, Shuster SA, Aguayo A, Hill EM, Kiani K, Ikpeazu J, Martinez JS, Purpura M, Smit AN, Patton DF, Mistlberger RE, Palmiter RD, Steele AD - Elife (2014)

Bottom Line: Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive.To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA.These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology, California Institute of Technology, Pasadena, United States.

ABSTRACT
Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.

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Higher fat content diet FAA studies in D1R KO mice.(A) Normalized high activity behavior of D1R KO (n = 6) and control (n = 8) mice on day 21 of 60% CR of breeder chow diet. (B) Normalized high activity behavior of D1R KO (n = 11) and control (n = 6) mice on day 21 of 60% CR on rodent high fat diet. (C) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR breeder chow. (D) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR high fat diet. The statistical test used was Mann–Whitney, where * indicates p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.03781.010
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fig4: Higher fat content diet FAA studies in D1R KO mice.(A) Normalized high activity behavior of D1R KO (n = 6) and control (n = 8) mice on day 21 of 60% CR of breeder chow diet. (B) Normalized high activity behavior of D1R KO (n = 11) and control (n = 6) mice on day 21 of 60% CR on rodent high fat diet. (C) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR breeder chow. (D) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR high fat diet. The statistical test used was Mann–Whitney, where * indicates p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.03781.010

Mentions: As D1R KO mice show low body weight on standard diets and have a decreased interest in feeding (Drago et al., 1994), one possible explanation for their lack of FAA on a 60% CR diet consisting of standard chow (5001 rodent chow; LabDiet) is that it was insufficiently palatable to induce wakefulness that is a prerequisite for FAA. Based on our prior work demonstrating that fatty foods are more potent inducers of FAA in mice than sugary foods (Hsu et al., 2010b; Gallardo et al., 2012), we tested whether D1R KO mice would show FAA for a 60% CR diet consisting of a more palatable, fat-rich diet. We fed D1R KO and WT controls a 60% CR diet of ‘breeder’ chow (5015 mouse diet; LabDiet), which has 25.3% calories from fat (5001 rodent chow has 13.5% calories from fat) at ZT 8 daily. D1R KO mice failed to show FAA for breeder chow, exerting only 4–8% of their total daily high activity behaviors in the 3 hr preceding scheduled meal time (Figure 4A,C). Interestingly, although WT mice showed FAA for breeder chow, it was attenuated compared to that observed with standard chow, as WT mice redistributed only ∼20% of high activity behaviors to the 3 hr preceding feeding (Figure 4A,C) compared to 30–40% on standard chow (Figure 2E). We also tested an even higher fat content chow, rodent ‘high fat diet’ (HFD), in which 60% of the calories come from fat. A 60% CR diet of HFD fed once daily at ZT 8 failed to induce FAA in D1R KO mice and induced a very modest FAA in WT controls, which allocated only about 10% of total high activity behaviors to the 3 hr preceding meal time (Figure 4B,D). From these experiments, we concluded that D1R KO mice do not fail to anticipate scheduled meal time due to a lack of palatability of the CR food source.10.7554/eLife.03781.010Figure 4.Higher fat content diet FAA studies in D1R KO mice.


Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice.

Gallardo CM, Darvas M, Oviatt M, Chang CH, Michalik M, Huddy TF, Meyer EE, Shuster SA, Aguayo A, Hill EM, Kiani K, Ikpeazu J, Martinez JS, Purpura M, Smit AN, Patton DF, Mistlberger RE, Palmiter RD, Steele AD - Elife (2014)

Higher fat content diet FAA studies in D1R KO mice.(A) Normalized high activity behavior of D1R KO (n = 6) and control (n = 8) mice on day 21 of 60% CR of breeder chow diet. (B) Normalized high activity behavior of D1R KO (n = 11) and control (n = 6) mice on day 21 of 60% CR on rodent high fat diet. (C) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR breeder chow. (D) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR high fat diet. The statistical test used was Mann–Whitney, where * indicates p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.03781.010
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4196120&req=5

fig4: Higher fat content diet FAA studies in D1R KO mice.(A) Normalized high activity behavior of D1R KO (n = 6) and control (n = 8) mice on day 21 of 60% CR of breeder chow diet. (B) Normalized high activity behavior of D1R KO (n = 11) and control (n = 6) mice on day 21 of 60% CR on rodent high fat diet. (C) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR breeder chow. (D) Normalized high activity in the 3 hr preceding scheduled meal time for mice on a diet of 60% CR high fat diet. The statistical test used was Mann–Whitney, where * indicates p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.03781.010
Mentions: As D1R KO mice show low body weight on standard diets and have a decreased interest in feeding (Drago et al., 1994), one possible explanation for their lack of FAA on a 60% CR diet consisting of standard chow (5001 rodent chow; LabDiet) is that it was insufficiently palatable to induce wakefulness that is a prerequisite for FAA. Based on our prior work demonstrating that fatty foods are more potent inducers of FAA in mice than sugary foods (Hsu et al., 2010b; Gallardo et al., 2012), we tested whether D1R KO mice would show FAA for a 60% CR diet consisting of a more palatable, fat-rich diet. We fed D1R KO and WT controls a 60% CR diet of ‘breeder’ chow (5015 mouse diet; LabDiet), which has 25.3% calories from fat (5001 rodent chow has 13.5% calories from fat) at ZT 8 daily. D1R KO mice failed to show FAA for breeder chow, exerting only 4–8% of their total daily high activity behaviors in the 3 hr preceding scheduled meal time (Figure 4A,C). Interestingly, although WT mice showed FAA for breeder chow, it was attenuated compared to that observed with standard chow, as WT mice redistributed only ∼20% of high activity behaviors to the 3 hr preceding feeding (Figure 4A,C) compared to 30–40% on standard chow (Figure 2E). We also tested an even higher fat content chow, rodent ‘high fat diet’ (HFD), in which 60% of the calories come from fat. A 60% CR diet of HFD fed once daily at ZT 8 failed to induce FAA in D1R KO mice and induced a very modest FAA in WT controls, which allocated only about 10% of total high activity behaviors to the 3 hr preceding meal time (Figure 4B,D). From these experiments, we concluded that D1R KO mice do not fail to anticipate scheduled meal time due to a lack of palatability of the CR food source.10.7554/eLife.03781.010Figure 4.Higher fat content diet FAA studies in D1R KO mice.

Bottom Line: Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive.To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA.These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology, California Institute of Technology, Pasadena, United States.

ABSTRACT
Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.

Show MeSH