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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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Mice were injected i.p. with either SKF-81297 (n = 8–12) or water (n = 8–12) for 14 days and deprived of food each day for 4 hr post-injection to prevent any drug-induced food consumption.(A) High activity in the 3 hr preceding daily injection on days 0, 7, and 14 of the experiment. (B) Quantitation of c-Fos immunostaining in the dorsal striatum of D1R WT (n = 2) and D1R KO (n = 2). (C) A low magnification (D) and at 10×. (E) c-Fos immunostaining in the dorsal striatum of a D1R KO mouse, a low magnification (F) and at 10×.DOI:http://dx.doi.org/10.7554/eLife.03781.021
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fig12s1: Mice were injected i.p. with either SKF-81297 (n = 8–12) or water (n = 8–12) for 14 days and deprived of food each day for 4 hr post-injection to prevent any drug-induced food consumption.(A) High activity in the 3 hr preceding daily injection on days 0, 7, and 14 of the experiment. (B) Quantitation of c-Fos immunostaining in the dorsal striatum of D1R WT (n = 2) and D1R KO (n = 2). (C) A low magnification (D) and at 10×. (E) c-Fos immunostaining in the dorsal striatum of a D1R KO mouse, a low magnification (F) and at 10×.DOI:http://dx.doi.org/10.7554/eLife.03781.021

Mentions: We repeated this experiment, omitting caffeine, and prevented food intake for 4 hr post-injection to control for drug-induced feeding as a potential factor for inducing anticipatory activity in the experiment described above. To that end, mice were injected daily for 14 days with either SKF-81297 (n = 12) or water (n = 12). We observed significant (p < 0.05) behavioral entrainment by the 14th day of injection (Figure 12—figure supplement 1). To confirm that the SKF-81297 was activating D1R neurons, we injected n = 2 D1R WT and D1R KO mice with drug and euthanized them 1 hr after injection, processing their brains of c-Fos immunostaining. We noted a marked number of cells staining in the dorsal striatum of WT but not the D1R KO mice (Figure 12—figure supplement 1).


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)

Mice were injected i.p. with either SKF-81297 (n = 8–12) or water (n = 8–12) for 14 days and deprived of food each day for 4 hr post-injection to prevent any drug-induced food consumption.(A) High activity in the 3 hr preceding daily injection on days 0, 7, and 14 of the experiment. (B) Quantitation of c-Fos immunostaining in the dorsal striatum of D1R WT (n = 2) and D1R KO (n = 2). (C) A low magnification (D) and at 10×. (E) c-Fos immunostaining in the dorsal striatum of a D1R KO mouse, a low magnification (F) and at 10×.DOI:http://dx.doi.org/10.7554/eLife.03781.021
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4196120&req=5

fig12s1: Mice were injected i.p. with either SKF-81297 (n = 8–12) or water (n = 8–12) for 14 days and deprived of food each day for 4 hr post-injection to prevent any drug-induced food consumption.(A) High activity in the 3 hr preceding daily injection on days 0, 7, and 14 of the experiment. (B) Quantitation of c-Fos immunostaining in the dorsal striatum of D1R WT (n = 2) and D1R KO (n = 2). (C) A low magnification (D) and at 10×. (E) c-Fos immunostaining in the dorsal striatum of a D1R KO mouse, a low magnification (F) and at 10×.DOI:http://dx.doi.org/10.7554/eLife.03781.021
Mentions: We repeated this experiment, omitting caffeine, and prevented food intake for 4 hr post-injection to control for drug-induced feeding as a potential factor for inducing anticipatory activity in the experiment described above. To that end, mice were injected daily for 14 days with either SKF-81297 (n = 12) or water (n = 12). We observed significant (p < 0.05) behavioral entrainment by the 14th day of injection (Figure 12—figure supplement 1). To confirm that the SKF-81297 was activating D1R neurons, we injected n = 2 D1R WT and D1R KO mice with drug and euthanized them 1 hr after injection, processing their brains of c-Fos immunostaining. We noted a marked number of cells staining in the dorsal striatum of WT but not the D1R KO mice (Figure 12—figure supplement 1).

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