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Winter blues and summer bummer link brains of rats and man

Diseases and IllnessesUC DavisParkinson's Disease

Nicholas Spitzer and Davide Dulcis felt for people in higher latitudes whose attitudes soured in the shorter daylight hours of winter.

The neuroscientists, who work in balmy San Diego, wondered whether summer was a bummer for rats. They’re nocturnal, after all.

That thought experiment has led the researchers to discover that an adult mammal’s brain can “rewire” itself in response to light by recruiting brain cells to change the signaling chemical they ordinarily produce.

Their research, published Thursday in the journal Science, offers hints toward new avenues of research into Parkinson's disease, stroke, addiction and depression.

Dulcis and Spitzer had already tinkered lower in the evolutionary ladder, showing that neurons in frogs switched transmitters - including one that determined pigment.

This time, they spent weeks subjecting rats to varied durations of sunlight. Then they put them in a maze and swimming pool to see whether different daylight hours changed how stressed they were about making decisions, and how quickly they gave up trying to get out of the water.

"We strongly suspected we would see the same sorts of things" as humans exhibited, Spitzer said.

The rats did not disappoint them. The two were surprised, however, when they took a close look at the rats' hypothalamus, a region of the brain that regulates the body's limbic system, the center of our instinctive behaviors.

In areas of the hypothalamus, the number of neurons producing dopamine and somatostatin (important regulators of learning and emotion) varied like a see-saw. So did the number of receptors. It appeared that other neurons had been enlisted to help out their dopamine-dispensing compatriots. The adult brain circuitry was more flexible, and neurons were not fated to produce just one neurotransmitter, the two concluded.

"We realized light must be doing something to the brain," Dulcis said. "We didn’t expect depression to be related to dopamine."

The two then cut off these new neuronal recruits to see whether behaviors changed. The mice responded as if their daylight hours had been altered. When the mice were returned to light therapy, their behavior reverted.

"Not only do you see these anatomical structures, but you see changes in behavior," Spitzer said. "We’re not talking about a developing mammal. We’re talking about an adult brain."

The two identified an enzyme linked with the switching, but the mechanism for how that chain of events begins remains a mystery.

"Even if we don’t know the mechanism, in reality the brain knows how to work the engine and make the switch," Dulcis said. "This concept of switching and replenishing is a new one."

The researchers hope to shift colleagues away from the mainstream approach of “tweaking” numbers and strength of neurons and synapses.

Neuronal switching, they suggest, may one day lead to a therapy that incorporates new circuitry in the brains of patients suffering from the dopamine depletion of Parkinson’s disease. The same neurotransmitter, which regulates reward-based learning, is implicated in addiction. And there could be other undiscovered switching relationships that could steer research into depression or post-traumatic stress, Spitzer said.

Other scientists who have done similar research are listening.

"In science, there are many dogmas and one of them is that the neuronal identity is fated even before the neuron is born," said Laura Borodinsky, a UC Davis neuroscientist. "The authors of this study make a remarkable contribution to prove this dogma wrong."

Copyright © 2014, The Baltimore Sun
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