At every waking moment, your brain is juggling two very different sets of information. Input from the world around you, like sights and smells, has to be processed. But so does internal information — your memories and thoughts. Right now, for example, I’m looking at a peach: It’s yellow and pink, and has a lot of fuzz. But I also know that it smells nice (a personal assessment) and I’m imagining how good it will taste, based on my previous experience with fragrant pink fruits.
The brain’s ability to handle these different signals is key to cognitive function. In some disorders, particularly autism and schizophrenia, this ability is disrupted. The brain has difficulty keeping internal and external input straight.
In a new study published Thursday in Cell, researchers observe the switching method in action for the first time. While the research used mice, not humans, principal investigator and NYU Langone Medical Center assistant professor Michael Halassa sees this as a huge step toward understanding and manipulating the same functions in humans.
“This is one of the few moments in my life where I’d actually say yes, absolutely this is going to translate to humans,” Halassa said. “This isn’t something based on genes or molecules that are specific to one organism. The underlying principles of how the brain circuitry works are likely to be very similar in humans and mice.”
That circuitry has been hypothesized for decades. Neurologists know that the cortex of the brain is responsible for higher cognitive functions, like music and language. And the thalamus, which is an egg-like structure in the center of the brain, works to direct the flow of internal and external information before it gets to the cortex. In the 1980s, Francis Crick (known as the father of DNA) suggested that if the thalamus was the gateway to the cortex, the thin layer between them — called the thalamic reticular nucleus (TRN) — served as the guardian of that gateway.
The issue with proving this has been mostly technical, Halassa said, because it’s difficult to watch an animal switch from one processing mode to another. In the new paper, Halassa and his colleagues developed experimental protocols for doing just that. The researchers identified TRN cells and studied how they changed during sleep, when brain activity is internal. The results, they wrote, suggest that the cells block visual information from getting to the cortex while mice sleep, but ferry it along when the mouse is awake and concentrating.
By manipulating these cells, the researchers were able to flip those switches in the waking brain, too: Sleep-deprived mice were suddenly better at finding food when TRN cells were set to waking mode, and well-rested mice did poorly at the same task when TRN cells mimicked their sleeping function.
Now Halassa and his colleagues will collaborate with other researchers to find the same mechanism in humans. If the same circuitry is there, it could mean new treatments for autism and schizophrenia. “We haven’t really developed new therapeutics for these disorders for the past 50 years,” Halassa said. He and other researchers will now use TRN manipulation in mice whose brains mimic human disorders.
The new treatments could come in the form of drugs that target these particular neurons, according to Halassa, but deep brain stimulation, which can now be done non-invasively, could also prove helpful. And in patients who are profoundly disabled by their symptoms, an implantable device to fix this circuitry might even be a solution.