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

Christian M Gallardo,Jonathan Ikpeazu,Chris H Chang,Andrew D Steele,Ralph E Mistlberger,Johan S Martinez,Andrea N Smit,Mari Purpura,Timothy F Huddy,Mateusz Michalik,Richard D Palmiter,Antonio Aguayo,Karun Kiani,Elizabeth M Hill,Martin Darvas,Mia Oviatt,Emily E Meyer,Danica F Patton,Scott A Shuster

doi:10.7554/elife.03781

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.

Highlights

Circadian (∼24 hr) rhythms of behavior and physiology are regulated by a distributed system of cellautonomous circadian oscillators located in the brain and in most peripheral organs and tissues (BellPedersen et al, 2005; Mohawk et al, 2012)
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
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 food anticipatory activity (FAA) on a 60% CR meal

Summary

Introduction

Circadian (∼24 hr) rhythms of behavior and physiology are regulated by a distributed system of cellautonomous circadian oscillators located in the brain and in most peripheral organs and tissues (BellPedersen et al, 2005; Mohawk et al, 2012). This is readily demonstrated by restricting food access to the middle of the light period, when nocturnal rodents normally eat little and are inactive. This induces a marked shifting of circadian oscillators and organ functions to align with the new daily feeding time, while the SCN remains coupled to the light-dark (LD) cycle.

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Results

Conclusion