Decision letter: Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice

Abstract

If you have ever traveled a long distance by plane, you will likely be familiar with jet lag. This disorientating sensation occurs because our brains have ‘internal clocks’ that keep track of the day–night cycle and control when we feel most tired or most alert. Flying rapidly from one time zone to another causes this clock to fall out of sync with the local time. It then takes time for the brain's clock to slowly adjust by responding to the levels of light and dark in the new environment. Humans—and other animals, plants, and even algae—have similar internal clocks, which are used to control behavior and predict events, such as the timing of a meal. These clocks can be set based on previous experiences of when food has been available and can be independent of those that follow the daily cycle of light and dark. Mice, for example, have internal clocks that make them more active at night and sleep during the day. However, if food is only provided during the day—say, at 2 o'clock in the afternoon—hungry mice will quickly adjust when they are awake in order to get the food as soon it is provided. Also, for a few hours before their new feeding time the mice will tend to jump and move around more; this is known as ‘food anticipatory activity’. Researchers have been studying this activity for around 40 years, but the specific regions of the brain and the processes that support these rhythms of feeding behavior remained unknown. Now, Gallardo et al. have shown that mice need dopamine—a neurotransmitter that is often called the brain's ‘feel-good chemical’—to maintain the internal clock that supports food anticipatory activity. Neurotransmitters are chemicals that carry signals between neurons; one neuron releases the chemical, and another detects it using proteins on the neuron's surface called receptors. Two main types of receptors—called D1 receptors and D2 receptors—detect dopamine. Gallardo et al. found that D1 receptors are important for maintaining feeding-related daily rhythms, but that D2 receptors are not. Additionally, dopamine only needs to be produced in a region of the brain called the dorsal striatum for food anticipatory activity to occur. This suggests that only D1 receptors in this region influence this activity, though there are many other regions of the brain that contain these receptors. The next challenge is to unravel the neural circuits that control food anticipation behavior. For example, what ‘tells’ the neurons in the dorsal striatum that an animal is hungry? Which of the D1 receptor expressing neurons relay the information about the timing of food anticipatory behavior and to where? Also, if a similar clock operates in humans, testing to see if it is misregulated in people with eating disorders could help us to better understand these conditions.