Floyd Bloom: Building a bridge to the future  pg. 5

Pedals of the piano

Bloom was particularly intrigued by norepinephrine, a neurotransmitter related to adrenaline that causes blood to vessels to constrict and the heart to beat more forcefully and rapidly, and he began what he calls a career-long “obsession” with that neurotransmitter.

Initially focusing on the cerebral cortex, the center of higher mental functions in the brain, Bloom and his associates mapped out the pathway of norepinephrine-associated nerve fibers, and discovered that the origin of the fibers came from an area of the brainstem called the locus coeruleus. The researchers found that while other neurotransmitters directly affected the “excitability” of this small group of cells, norepinephrine worked by modulating other signals.

“It was a completely novel action, not predictable by anything that was previously known,” Bloom says. “Along with others, we were then able to extend that action to the hippocampus and other areas of the brain. (The finding) told us that norepinephrine does not convey specific information, but is more like the foot pedals on a piano. It changes the harmonics of the other information that’s going on. People like to call it a modulator instead of a transmitter. It is transmitting modulatory information. It’s enhancing, or in its absence, diminishing, the effectiveness of other inputs.”

At the electron microscope at the Scripps Research Institute in 1987.
Courtesy of Floyd Bloom
With a better grasp of these novel chemical pathways, investigators began relating synaptic information to behavioral responses, such as depression, and then biochemically lacing those responses with epinephrine, dopamine and serotonin. Those experiments, in turn, ultimately led to the development of such antidepressant drugs as Prozac. Citing other seminal work that he and Bloom completed together, Siggins says they were the first to dissect the neurophysiological effects of prostaglandins in the brain, the first to describe the actions of beta-endorphin in the brain, and the first to report a novel mechanism of action of brain endorphin and other opiate peptides, termed “disinhibition,” that could cause epilepsy-like effects.

Building on discoveries in the “norepinephrine days,” Bloom’s lab members were open to the notion that the brain has adapted many unusual ways of sending messages, which inspired them to search for other possible novel ways neurons communicate. “It put us in the right frame of mind to study brain peptides, for example,” Siggins says. “What we ultimately found with opiate peptides and virtually every other peptide we studied much later is that they all had their own unusual signature or fingerprint of action very different from the fast, rapidly-conducting classical pathways. And Floyd had this intuition early on that the peptides were the wave of the future.”

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