Neurons that control brain's body clock identified!

Modern society often places abnormal pressure on the human body -- from shifting time schedules due to air travel, to work cycles that don't conform to natural light, to odd eating times -- and these external conditions create an imbalance in the body's natural cycles, which are evolutionarily synchronized to day and night. These imbalances may contribute to depression, obesity, cardiovascular diseases and even cancer.

Neurons in the brain that produce the pleasure-signaling neurotransmitter dopamine also directly control the brain's circadian center, or "body clock" - the area that regulates eating cycles, metabolism and waking/resting cycles - a key link that possibly affects the body's ability to adapt to jet lag and rotating shift work, a new study has demonstrated in the journal Current Biology.

"This discovery, which identifies a direct dopamine neuron connection to the circadian center, is possibly the first step toward the development of unique drugs, targeting specific neurons, to combat the unpleasant symptoms of jet-lag and shiftwork, as well as several dangerous pathologies," said the senior author of the study.

"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," senior author said. "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."

Sleep disorders and abnormal circadian rhythms affecting the brain and other organs can worsen many pathologies involving aberrant dopamine neurotransmission, senior author said, including Parkinson's disease, depression, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia and drug addiction.

The researchers used two types of mice in their investigation: one normal, the other with dopamine signaling disrupted. By shifting the light schedules of the two groups by six hours, a jet-lag effect, they found that the dopamine-disrupted animals took much longer to resynchronize to the six-hour time shift, indicating feedback between the dopamine neurons and the circadian center.

Authors identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN). They demonstrate that D1 dopamine receptor (Drd1) signaling within the SCN is necessary for properly timed resynchronization of activity rhythms to phase-shifted light:dark cycles and that elevation of DA tone through selective activation of VTA DA neurons accelerates photoentrainment.

These findings demonstrate a previously unappreciated role for direct DA input to the master circadian clock and highlight the importance of an evolutionarily significant relationship between the circadian system and the neuromodulatory circuits that govern motivational behaviors.

"This shows that when we engage in rewarding activities like eating, we are inadvertently affecting our biological rhythms," senior author said. "We may have found the missing link to how pleasurable things and the circadian system influence one another."

http://www.cell.com/current-biology/abstract/S0960-9822(17)30857-6