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 acutely fasted D1R KO and WT mice.(A) Total number of seconds of high intensity activity (walking, hanging, jumping, or rearing) for D1R KO (n = 6 KO) and WT (n = 12) mice on 3 consecutive days of ad libitum diet. (B) Total number of seconds of high intensity activity for D1R KO (n = 7) and WT (n = 14) mice on 3 consecutive days. On day 1 and day 2 all mice were on an ad libitum diet, but on the third day all mice were deprived of food. (C) The ratio of total seconds of high activity on day 3 divided by total seconds of high activity on day 2. Bars show medians and interquartile ranges. The statistical test used was Mann–Whitney, where ** indicates p < 0.01.DOI:http://dx.doi.org/10.7554/eLife.03781.011
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Activity of acutely fasted D1R KO and WT mice.(A) Total number of seconds of high intensity activity (walking, hanging, jumping, or rearing) for D1R KO (n = 6 KO) and WT (n = 12) mice on 3 consecutive days of ad libitum diet. (B) Total number of seconds of high intensity activity for D1R KO (n = 7) and WT (n = 14) mice on 3 consecutive days. On day 1 and day 2 all mice were on an ad libitum diet, but on the third day all mice were deprived of food. (C) The ratio of total seconds of high activity on day 3 divided by total seconds of high activity on day 2. Bars show medians and interquartile ranges. The statistical test used was Mann–Whitney, where ** indicates p < 0.01.DOI:http://dx.doi.org/10.7554/eLife.03781.011

Mentions: Because D1R KO mice failed to anticipate a variety of 60% CR meals fed once daily, we assessed whether this defect was due to an inability to cope with reduced calories. To address this issue, we employed an alternative assay for relating hunger status to activity levels by acutely fasting D1R KO and control mice. In previous studies of the home-cage behavioral response to acute fasting in WT C57BL/6J mice, mice increased their high-activity behaviors two-fold upon acute fasting as compared to AL food access (Gallardo et al., 2014). We measured the total high-activity behavior of D1R KO and WT controls over a 3-day period. During days 1 and 2, all mice had AL access to standard chow. As expected, D1R WT and D1R KO mice showed similar median levels of high activity behaviors over 3 days of AL diet (Figure 5A). On the third day, mice were either maintained on an AL diet or had their food removed entirely (‘fasted’). D1R KO mice showed a strong increase in high-activity behaviors upon acute food deprivation, increasing their activity to a greater extent than fasted WT mice, with mean values of 270.5 min and 376.9 min of high activity, respectively (Figure 5B). To normalize these data, we plotted the ratio of activity on fasting day 3 over that of AL day 2 (Figure 5C). This ratio is expected to be around one for mice that were not food deprived, in that the activity of an individual mouse should not vary much from day-to-day. Indeed, the amount of high activity on day 2 vs day 3 was close to one for both D1R WT (0.96) and D1R KO mice (0.92) (Figure 5C). However, when food deprived, WT mice had an activity ratio of 1.9 and D1R KO mice had a ratio of 2.5 (both of which were statistically significant when compared within genotype to AL, p < 0.01 Mann–Whitney). Importantly, this assay does not measure food timing, as these mice were naive to any feeding schedule. These results suggest that the D1R KO mice are capable of up-regulating activity in response to acute food deprivation (i.e., hunger), demonstrating an intact circuitry of detecting and responding to fasting and thus ruling out gross metabolic defects.10.7554/eLife.03781.011Figure 5.Activity of acutely fasted D1R KO and WT 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)

Activity of acutely fasted D1R KO and WT mice.(A) Total number of seconds of high intensity activity (walking, hanging, jumping, or rearing) for D1R KO (n = 6 KO) and WT (n = 12) mice on 3 consecutive days of ad libitum diet. (B) Total number of seconds of high intensity activity for D1R KO (n = 7) and WT (n = 14) mice on 3 consecutive days. On day 1 and day 2 all mice were on an ad libitum diet, but on the third day all mice were deprived of food. (C) The ratio of total seconds of high activity on day 3 divided by total seconds of high activity on day 2. Bars show medians and interquartile ranges. The statistical test used was Mann–Whitney, where ** indicates p < 0.01.DOI:http://dx.doi.org/10.7554/eLife.03781.011
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Activity of acutely fasted D1R KO and WT mice.(A) Total number of seconds of high intensity activity (walking, hanging, jumping, or rearing) for D1R KO (n = 6 KO) and WT (n = 12) mice on 3 consecutive days of ad libitum diet. (B) Total number of seconds of high intensity activity for D1R KO (n = 7) and WT (n = 14) mice on 3 consecutive days. On day 1 and day 2 all mice were on an ad libitum diet, but on the third day all mice were deprived of food. (C) The ratio of total seconds of high activity on day 3 divided by total seconds of high activity on day 2. Bars show medians and interquartile ranges. The statistical test used was Mann–Whitney, where ** indicates p < 0.01.DOI:http://dx.doi.org/10.7554/eLife.03781.011
Mentions: Because D1R KO mice failed to anticipate a variety of 60% CR meals fed once daily, we assessed whether this defect was due to an inability to cope with reduced calories. To address this issue, we employed an alternative assay for relating hunger status to activity levels by acutely fasting D1R KO and control mice. In previous studies of the home-cage behavioral response to acute fasting in WT C57BL/6J mice, mice increased their high-activity behaviors two-fold upon acute fasting as compared to AL food access (Gallardo et al., 2014). We measured the total high-activity behavior of D1R KO and WT controls over a 3-day period. During days 1 and 2, all mice had AL access to standard chow. As expected, D1R WT and D1R KO mice showed similar median levels of high activity behaviors over 3 days of AL diet (Figure 5A). On the third day, mice were either maintained on an AL diet or had their food removed entirely (‘fasted’). D1R KO mice showed a strong increase in high-activity behaviors upon acute food deprivation, increasing their activity to a greater extent than fasted WT mice, with mean values of 270.5 min and 376.9 min of high activity, respectively (Figure 5B). To normalize these data, we plotted the ratio of activity on fasting day 3 over that of AL day 2 (Figure 5C). This ratio is expected to be around one for mice that were not food deprived, in that the activity of an individual mouse should not vary much from day-to-day. Indeed, the amount of high activity on day 2 vs day 3 was close to one for both D1R WT (0.96) and D1R KO mice (0.92) (Figure 5C). However, when food deprived, WT mice had an activity ratio of 1.9 and D1R KO mice had a ratio of 2.5 (both of which were statistically significant when compared within genotype to AL, p < 0.01 Mann–Whitney). Importantly, this assay does not measure food timing, as these mice were naive to any feeding schedule. These results suggest that the D1R KO mice are capable of up-regulating activity in response to acute food deprivation (i.e., hunger), demonstrating an intact circuitry of detecting and responding to fasting and thus ruling out gross metabolic defects.10.7554/eLife.03781.011Figure 5.Activity of acutely fasted D1R KO and WT 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
Related in: MedlinePlus