Limits...
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.

Show MeSH

Related in: MedlinePlus

Activity of D2R KO mice and WT mice on 60% CR.(A) The fraction of all recorded frames within each 1-hr bin on day -7 when the mice were walking, hanging, jumping, or rearing. All mice were still on an ad libitum diet. (B, C, D) The fraction of high activity frames for D2R WT (n = 12) and KO (n = 8) mice in each 1-hr bin on days 14, 21, and 28 of CR. Arrows indicate the bin in which the calorie restricted meal was delivered (ZT 8). Shaded boxes represent lights-off and yellow boxes indicated lights on. (E) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) on days -7, 0, 7, 14, 21, and 28 of the study for mice on CR diets. (F) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) for mice on ad libitum diets. There were no significant differences (Mann–Whitney) in fraction of high activity between D2R WT and KO mice. Median data are plotted with error bars indicating interquartile ranges.DOI:http://dx.doi.org/10.7554/eLife.03781.003
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Activity of D2R KO mice and WT mice on 60% CR.(A) The fraction of all recorded frames within each 1-hr bin on day -7 when the mice were walking, hanging, jumping, or rearing. All mice were still on an ad libitum diet. (B, C, D) The fraction of high activity frames for D2R WT (n = 12) and KO (n = 8) mice in each 1-hr bin on days 14, 21, and 28 of CR. Arrows indicate the bin in which the calorie restricted meal was delivered (ZT 8). Shaded boxes represent lights-off and yellow boxes indicated lights on. (E) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) on days -7, 0, 7, 14, 21, and 28 of the study for mice on CR diets. (F) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) for mice on ad libitum diets. There were no significant differences (Mann–Whitney) in fraction of high activity between D2R WT and KO mice. Median data are plotted with error bars indicating interquartile ranges.DOI:http://dx.doi.org/10.7554/eLife.03781.003

Mentions: To determine the significance of the dopamine system in mediating FAA, we tested mice lacking either dopamine D1 receptors (D1R KO mice) or dopamine D2R receptors (D2R KO mice). First, we investigated whether mice lacking D2R (Kelly et al., 1997) showed impairments in FAA. We measured the baseline home-cage behavior using automated video-based behavior analysis (Steele et al., 2007) of D2R KO mice and wild-type (WT) littermates in their home-cage environment. Prior to any dietary intervention (‘day -7’), both groups of mice demonstrated normal nocturnal activity waveforms with no significant differences in any 1-hr bin and no increase in activity in the hours before Zeitgeber Time (ZT) 8 (on a 13:11 LD cycle, ZT 12 is lights-off by convention) (Figure 1A). Next, we tested their ability to time a daily 60% CR meal fed at ZT 8 every day for 28 days, recording their behavior weekly. Data were normalized by dividing the amount of high activity behavior in each hour by the total seconds of activity over the 24 hr video recording to express a fraction of high activity per hour. Measurements taken at 14, 21, and 28 days of CR revealed that both WT and D2R KO mice had a large increase in high activity (hanging, jumping, walking, and rearing) behaviors during the 3 hr preceding feeding time (Figure 1B–D). In both D2R KO and WT mice fed 60% CR daily, we observed similar acquisition and maintenance of FAA defined as normalized high activity in the 3 hr before feeding (ZT 5–8) (Figure 1E). As expected, mice of either genotype with ad libitum (AL) access to food showed very little high activity behavior in the hours preceding scheduled feeding when they were given an additional food pellet as a control for handling and disturbance (Figure 1F). These results suggest that D2R is not necessary for mediating FAA on a 60% CR meal.10.7554/eLife.03781.003Figure 1.Activity of D2R KO mice and WT mice on 60% CR.


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)

Activity of D2R KO mice and WT mice on 60% CR.(A) The fraction of all recorded frames within each 1-hr bin on day -7 when the mice were walking, hanging, jumping, or rearing. All mice were still on an ad libitum diet. (B, C, D) The fraction of high activity frames for D2R WT (n = 12) and KO (n = 8) mice in each 1-hr bin on days 14, 21, and 28 of CR. Arrows indicate the bin in which the calorie restricted meal was delivered (ZT 8). Shaded boxes represent lights-off and yellow boxes indicated lights on. (E) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) on days -7, 0, 7, 14, 21, and 28 of the study for mice on CR diets. (F) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) for mice on ad libitum diets. There were no significant differences (Mann–Whitney) in fraction of high activity between D2R WT and KO mice. Median data are plotted with error bars indicating interquartile ranges.DOI:http://dx.doi.org/10.7554/eLife.03781.003
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Activity of D2R KO mice and WT mice on 60% CR.(A) The fraction of all recorded frames within each 1-hr bin on day -7 when the mice were walking, hanging, jumping, or rearing. All mice were still on an ad libitum diet. (B, C, D) The fraction of high activity frames for D2R WT (n = 12) and KO (n = 8) mice in each 1-hr bin on days 14, 21, and 28 of CR. Arrows indicate the bin in which the calorie restricted meal was delivered (ZT 8). Shaded boxes represent lights-off and yellow boxes indicated lights on. (E) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) on days -7, 0, 7, 14, 21, and 28 of the study for mice on CR diets. (F) The fraction of high activity in the 3 hr before feeding time (ZT 5–8) for mice on ad libitum diets. There were no significant differences (Mann–Whitney) in fraction of high activity between D2R WT and KO mice. Median data are plotted with error bars indicating interquartile ranges.DOI:http://dx.doi.org/10.7554/eLife.03781.003
Mentions: To determine the significance of the dopamine system in mediating FAA, we tested mice lacking either dopamine D1 receptors (D1R KO mice) or dopamine D2R receptors (D2R KO mice). First, we investigated whether mice lacking D2R (Kelly et al., 1997) showed impairments in FAA. We measured the baseline home-cage behavior using automated video-based behavior analysis (Steele et al., 2007) of D2R KO mice and wild-type (WT) littermates in their home-cage environment. Prior to any dietary intervention (‘day -7’), both groups of mice demonstrated normal nocturnal activity waveforms with no significant differences in any 1-hr bin and no increase in activity in the hours before Zeitgeber Time (ZT) 8 (on a 13:11 LD cycle, ZT 12 is lights-off by convention) (Figure 1A). Next, we tested their ability to time a daily 60% CR meal fed at ZT 8 every day for 28 days, recording their behavior weekly. Data were normalized by dividing the amount of high activity behavior in each hour by the total seconds of activity over the 24 hr video recording to express a fraction of high activity per hour. Measurements taken at 14, 21, and 28 days of CR revealed that both WT and D2R KO mice had a large increase in high activity (hanging, jumping, walking, and rearing) behaviors during the 3 hr preceding feeding time (Figure 1B–D). In both D2R KO and WT mice fed 60% CR daily, we observed similar acquisition and maintenance of FAA defined as normalized high activity in the 3 hr before feeding (ZT 5–8) (Figure 1E). As expected, mice of either genotype with ad libitum (AL) access to food showed very little high activity behavior in the hours preceding scheduled feeding when they were given an additional food pellet as a control for handling and disturbance (Figure 1F). These results suggest that D2R is not necessary for mediating FAA on a 60% CR meal.10.7554/eLife.03781.003Figure 1.Activity of D2R KO mice and WT mice on 60% CR.

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
Related in: MedlinePlus