Researchers have identified some of the brain cells that control our body's internal clock. The findings provide new insights into how the human body responds to jet lag, as well as into why it is so difficult to switch off your favorite show and go to sleep.
A team of researchers from the University of Virginia (UVA) in Charlottesville set out to examine the neurological underpinnings of our so-called body clock.
The phrase "biological clock" refers to the "center" that controls the different groups of interacting molecules that are found throughout the human body.
These different groups are controlled by a main "master clock" consisting of neurons located in an area of the brain called the suprachiasmatic nucleus (SCN). The SCN is found in the brain's hypothalamus, and it consists of more than 20,000 neurons.
The new research identifies additional neurons that play a key role in regulating our bodily rhythms. Specifically, the new study - published in the journal Current Biology - finds that dopamine-producing neurons have a direct connection to the brain's SCN.
Dopamine is a neurotransmitter that controls pleasure signaling, learning, and movement. It also helps the brain to process rewards, as well as to detect when food or a sexual partner is available.
Although it has deep biological roots, the activity of the body clock is also regulated by external stimuli, such as light and darkness.
The new findings may help researchers to better understand how phenomena such as jet lag or shift work affect the body, and to come up with better therapies for these effects.
The research was overseen by Ali Deniz Güler, a UVA professor of biology and neuroscience whose laboratory hosted the study, and the first author of the paper is Ryan Grippo, a Ph.D. candidate and student of Prof. Güler's.
Studying dopamine signaling in mice
Grippo and team examined two groups of mice.
One group was genetically modified to have a disrupted dopamine circuit, and the other group was kept as a normal control group.
More specifically, the first group of mice had the dopamine receptor signaling within the SCN genetically knocked off - that is, there was no communication between dopamine neurons in the brain's so-called ventral tegmental area (VTA) and the SCN.
Next, the researchers altered the light schedules of the two groups of mice by 6 hours, recreating the conditions of jet lag.
The genetically modified group of mice was much slower to adapt to the schedule shift compared with its control counterparts. This indicated to the researchers that dopamine signaling between the VTA and the SCN is necessary for circadian rhythm regulation.
Because of dopamine's role in processing rewards, these findings offer unique insights into how our body clock works.
Referring to the strengths and limitations of the study, Prof. Güler told Medical News Today:
"We have used both genetic and actuator technologies that allowed us to control the expression of the dopamine receptor that is expressed in the [SCN] as well as the activity of the neurons that express the receptor specifically. This multi-pronged approach is what allowed us to uncover the long sought after connection that has been missed previously."
However, the researcher noted that more work is needed to determine "the precise ethological significance of this connection both in [the study's] model system (mouse) and other mammals."
'Rewarding activities' affect the body clock
The new study may help to explain why it seems particularly difficult to go to bed early when we are watching our favorite TV show. As Prof. Güler explains:
This shows that when we engage in rewarding activities like eating, we are inadvertently affecting our biological rhythms [...]. We may have found the missing link to how pleasurable things and the circadian system influence one another."
Prof. Ali Deniz Güler
Prof. Güler further comments on the significance of the findings, saying:
"Scientists have been working for decades to help the body's circadian system readily re-synchronize to variable work and eating schedules and flights across multiple time zones."
"Although it has been thought that the circadian system and the dopaminergic system [interact], the nature of this interaction has been quite elusive until our discovery," Prof. Güler told MNT.
"Finding this connection between dopamine-producing neurons and the circadian center allows us to target these neurons with therapies that could potentially provide relief of symptoms for travelers and shift workers particularly, and possibly people with insomnia," he says.
Prof. Güler is not only hopeful that the findings will lead to new drugs for these pathologies, but he also thinks the findings provide insights into a whole other range of conditions.
"We believe we have a novel insight into how circadian system behaviors, like sleeping, are affected by the dopaminergic pathologies including Parkinson's disease, ADHD, etc. We are also interested in understanding how circadian system in return affect these pathologies," the lead researcher told us.