Serotonin is a neurotransmitter, or chemical messenger, that mediates many complex processes in the brain. It’s perhaps best known for its role in regulating mood. It’s also thought to help regulate several life-sustaining functions, such as breathing. Serotonin is produced by nerve cells in the lower brain, or brain stem.
To learn more about how serotonin-producing neurons affect essential life processes, Dr. Susan Dymecki of Harvard Medical School and her colleagues used a sophisticated genetic technique to selectively and reversibly silence serotonin-producing nerve cells in living mice. The study received major funding from NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), with additional support from other NIH components.
The researchers used a method they’d previously developed, called intersectional genetics, to generate an additional type of receptor on the surfaces of nerve cells that produce serotonin. The specialized receptor, not found in nature, was developed by NIH-funded researcher Dr. Bryan Roth and his colleagues. It binds specifically to a man-made chemical called clozapine-N-oxide (CNO). Dymecki and her co-workers showed that this binding and receptor-triggering can deactivate serotonin-producing cells, effectively switching off communications in the serotonin network. CNO doesn’t normally affect cells in the animals’ brains or bodies. By injecting CNO into mice producing the receptor, the researchers could assess the effects of temporarily shutting down serotonin-producing neurons.
As reported in the July 29, 2011, edition of Science, the researchers exposed both normal mice and mice with the CNO receptor to elevated levels of carbon dioxide. Carbon dioxide buildup can lead to loss of consciousness. Normal mice almost immediately began to breathe faster and more deeply, releasing carbon dioxide through their lungs. Switching off the serotonin-producing neurons in the altered mice led to a much smaller response to carbon dioxide.
In another set of experiments, the researchers found that switching off the serotonin-producing neurons disrupted maintenance of a healthy body temperature. When the room temperature was set at 74 °F, normal mice could stabilize their body at the typical 98.6 °F. But the body temperatures of mice with the switched-off neurons quickly plunged to match the 74° room temperature.
“By selectively switching off the serotonin-producing cells, we can get a definite idea of what bodily functions the serotonin cells specifically control” Dymecki says. In future studies, she and her colleagues plan to add the CNO receptor to specific subsets of serotonin-producing neurons. Their goal is to better understand the role these neurons play in health and disorders such as SIDS and depression.