A fascinating study from scientists at Rockefeller University has shed new light on a deep brain mechanism that can stimulate awareness and cognition. The research homes in on a collection of giant neurons in the brain that seem to be able to modulate stimulation of the entire central nervous system.

One of the most fundamental, low-level states of consciousness is called generalized arousal (GA). This elemental state of the central nervous system is what we enter when we wake up in the morning, and the higher our levels of GA, the more sensitive and aware we are to external sensory stimuli.

The new study focuses on an area deep in the brainstem called the nucleus gigantocellularis (NGC), referred to by the researchers as "the black box" due to how little science currently understands of its function. The NGC is so named due to its unique congregation of giant, oversized neurons with links to the entire nervous system. While these giant NGC neurons are known to be crucial to elevations in GA, exactly how this occurs been a mystery.

"If you just look at the morphology of NGC neurons, you know they're important," says Donald Pfaff, head of the Neurobiology and Behavior lab at Rockefeller. "It's just a question of what they're important for. I think they're essential for the initiation of any behavior."

The first thing the scientists discovered was that these NGC neurons express an enzyme that produces nitric oxide, a chemical that relaxes blood vessels and increases tissue oxygenation. These are the only neurons in the brain that are known to produce this particular enzyme and, conveniently, they are all located very close to blood vessels.

"We're pretty sure that if these neurons need more oxygen and glucose, they will release nitric oxide into these nearby blood vessels in order to get it," says Pfaff.

The next step was to investigate what external stimuli cause these NGC neurons to produce increased volumes of nitric oxide. The researchers examined what happens when mice are introduced to changes in their environment. They found that when unfamiliar scents were deployed into an environment, NGC neurons in the mouse brains triggered increased levels of nitric oxide. This confirmed to the researchers that this NGC neuronal mechanism does seem to modulate GA levels.

"There is some low level of production when the animal is in a familiar setting," explains first author on the study, Inna Tabansky, "which is what you expect as they maintain arousal. But it is vastly increased when the animal is adapting to a new environment."

As well as offering a compelling new insight into how our brains potentially modulate different levels of consciousness and alertness, the study's findings could lead to fascinating new insights into psychiatric diseases. The specific gene that is related to the enzyme that triggers this nitric oxide release has been implicated in some mental disorders including bipolar and suicidal ideation. An interesting hypothesis raised by the study is that mutations in this gene could inhibit nitric oxide production, and result in dysregulated behavioral arousal. This could be associated with several psychiatric disorders that manifest in irregular responses to changes in environmental stimuli.

"By showing that this gene and its associated pathways have a particular role, at least in the rodent brain, that relates to a fundamental function of the nervous system, is a hint about how this gene can cause psychiatric disease," says Tabansky. "It's very preliminary, and there is a lot more work to be done, but it potentially opens a new way to study how this gene can alter an individual's psychology."

The study was published in the journal PNAS.