Researchers have developed a novel method for tracking the activity of small molecules in the brain, including the neurotransmitters serotonin and dopamine. Pairing tiny artificial receptors with semiconductor devices that are able to function in living tissue, the team was able to observe brain chemicals at a high level of detail.
The research, published in the journal Science, is part of the BRAIN Initiative, a large-scale collaboration among government, private industry, nonprofits, and numerous colleges and universities.
"Understanding the fundamentals of how neurotransmission occurs will help us understand not only how our brains work, but what's going on in psychiatric disorders," said lead researcher. "In order to move forward with dramatically better treatments, we need to understand how we encode information about anxiety or mood--processes that can go awry, sometimes with devastating consequences."
Researchers envisioned coupling artificial receptors with a nanoscale signaling platform. A major hurdle, however, was that the required transistors, which are basic units of computers and cell phones, and are needed to process a signal, don't work well in wet, salty environments.
"The workhorse of any transistor is the semiconductor," the lead researcher said. "But when you put it in salt water, the salt ions--charged atoms--line up on the semiconductor surface, and shield it, preventing detection of electric field changes. The question was, 'How can we tap into the powerful science and sensitivity of existing transistors to use them in high-salt environments like the brain?'
"Our breakthrough was that we used a different kind of receptor that was biologically inspired--after all, life began with RNA," the lead author said. "The Columbia investigators develop nucleic acid sequences that act as receptors, called aptamers, which are small enough that some part is close to semiconductor surfaces. And in this, we've overcome the 'salt shielding' problem."
Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection.
In the new paper, the team successfully identified and tested receptors for serotonin, dopamine, and glucose. The receptors were found to be extremely selective, binding only the molecules they were designed to bind. The system was successful even in living brain tissue from mice.
The method is universal, so it can be used for almost any target--to learn, for instance, how drugs change with time in the brain or other organs, how blood pressure is regulated, and how signaling molecules associated with the gut microbiome ebb and flow.
The team is now testing the strategy to watch neurochemicals in the brains of behaving animals.