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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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Cued handling FAA.(A) High activity data (in seconds) in 5 min bins for D1R KO (n = 7) and D1R WT (n = 8) mice that were disturbed 2 hr prior to scheduled feeding. (B) High activity data (in seconds) in 5 min bins for timed, calorie restricted D1R KO (n = 6) and D1R WT (n = 7) mice. Mice were disturbed 2 hr prior to feeding. (C) Summed high activity data over the cued period. The statistical test used was Mann–Whitney, where * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.DOI:http://dx.doi.org/10.7554/eLife.03781.012
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fig6: Cued handling FAA.(A) High activity data (in seconds) in 5 min bins for D1R KO (n = 7) and D1R WT (n = 8) mice that were disturbed 2 hr prior to scheduled feeding. (B) High activity data (in seconds) in 5 min bins for timed, calorie restricted D1R KO (n = 6) and D1R WT (n = 7) mice. Mice were disturbed 2 hr prior to feeding. (C) Summed high activity data over the cued period. The statistical test used was Mann–Whitney, where * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.DOI:http://dx.doi.org/10.7554/eLife.03781.012

Mentions: Having noted that some D1R KO mice had a small amount of FAA on a 60% CR diet (note the interquartile range in Figure 2B–E) and that D1R KO mice increased their activity when acutely fasted, we sought to further prompt FAA timing in D1R KO mice. We intentionally cued the D1R KO and control mice to expect food by entering the room in which they were being video recorded and disturbing their cage lids 2 hr in advance () of actual feeding time. We expected that this ‘cue’ would alert D1R KO mice and perhaps facilitate FAA. We cued D1R WT and KO mice on an AL diet to assay the amount of activity that occurs as the result of a disturbance independent of FAA. We observed a small increase in high activity behaviors lasting only 10 min post-cue in both D1R WT and D1R KO mice; there were no significant differences in the amount of activity induced in D1R WT and KO mice (Figure 6A). D1R KO mice on a CR diet did not show a sustained increase in activity after being cued to feeding time; their activity lasted only ∼10 min subsequent to the cue (Figure 6B). WT control mice on a CR diet showed a large increase in activity induced by the cue, or were already demonstrating FAA at the time of the cue, and sustained their increased activity for the following 2 hr (Figure 6B). Summation of the time of high-activity behavior 2 hr prior to feeding demonstrated a significant increase in activity in WT mice when CR compared to AL feeding, but not in D1R KO mice (Figure 5C). These results suggest that even cuing the D1R KO mice to the subsequent availability of food did not trigger FAA behaviors.10.7554/eLife.03781.012Figure 6.Cued handling FAA.


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)

Cued handling FAA.(A) High activity data (in seconds) in 5 min bins for D1R KO (n = 7) and D1R WT (n = 8) mice that were disturbed 2 hr prior to scheduled feeding. (B) High activity data (in seconds) in 5 min bins for timed, calorie restricted D1R KO (n = 6) and D1R WT (n = 7) mice. Mice were disturbed 2 hr prior to feeding. (C) Summed high activity data over the cued period. The statistical test used was Mann–Whitney, where * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.DOI:http://dx.doi.org/10.7554/eLife.03781.012
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4196120&req=5

fig6: Cued handling FAA.(A) High activity data (in seconds) in 5 min bins for D1R KO (n = 7) and D1R WT (n = 8) mice that were disturbed 2 hr prior to scheduled feeding. (B) High activity data (in seconds) in 5 min bins for timed, calorie restricted D1R KO (n = 6) and D1R WT (n = 7) mice. Mice were disturbed 2 hr prior to feeding. (C) Summed high activity data over the cued period. The statistical test used was Mann–Whitney, where * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.DOI:http://dx.doi.org/10.7554/eLife.03781.012
Mentions: Having noted that some D1R KO mice had a small amount of FAA on a 60% CR diet (note the interquartile range in Figure 2B–E) and that D1R KO mice increased their activity when acutely fasted, we sought to further prompt FAA timing in D1R KO mice. We intentionally cued the D1R KO and control mice to expect food by entering the room in which they were being video recorded and disturbing their cage lids 2 hr in advance () of actual feeding time. We expected that this ‘cue’ would alert D1R KO mice and perhaps facilitate FAA. We cued D1R WT and KO mice on an AL diet to assay the amount of activity that occurs as the result of a disturbance independent of FAA. We observed a small increase in high activity behaviors lasting only 10 min post-cue in both D1R WT and D1R KO mice; there were no significant differences in the amount of activity induced in D1R WT and KO mice (Figure 6A). D1R KO mice on a CR diet did not show a sustained increase in activity after being cued to feeding time; their activity lasted only ∼10 min subsequent to the cue (Figure 6B). WT control mice on a CR diet showed a large increase in activity induced by the cue, or were already demonstrating FAA at the time of the cue, and sustained their increased activity for the following 2 hr (Figure 6B). Summation of the time of high-activity behavior 2 hr prior to feeding demonstrated a significant increase in activity in WT mice when CR compared to AL feeding, but not in D1R KO mice (Figure 5C). These results suggest that even cuing the D1R KO mice to the subsequent availability of food did not trigger FAA behaviors.10.7554/eLife.03781.012Figure 6.Cued handling FAA.

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